Nūnū lawe leka o Kahului

Letter-carrying pigeon of Kahului.

In 1893 carrier pigeons arrived at Kahului, Maui. One was brought to Honolulu and released with a letter tied to its neck. It flew back to Kahului. This was of such great interest to the people that a song was written, and a quilt designed to commemorate the event.

ʻŌlelo Noʻeau, compiled by Mary Kawena Pukui, #2351

Introduction

Figure 17.1: Pigeon-Gram

In contrast to the nervous system, the endocrine system uses various chemical messengers called hormones that are released into the bloodstream. Hormones are molecular messengers that travel to target tissues and allow tissues that secrete hormones to influence the actions of their target tissues. The endocrine system is made up of all the tissues and organs that release these hormones. This chapter will explore the anatomical structures of the endocrine system and their functional organization. The chapter will further explain the different chemical makeup of each hormone and the influence each has on various tissues to help the body maintain homeostasis.

Cultural Connection: Māhū in Hawaiʻi

In traditional Hawaiian culture, māhū are individuals that embody both male and female spirits. Māhū are considered by some to be a third gender, essentially representing the feminine and masculine traits that exist in each of us. The concept of mix-gender or transgender individuals in Hawaiʻi is even mentioned in the sacred Kumulipo text. Traditionally, Māhū were not only accepted in Hawaiian society but were given specific roles and practices, to support overall society balance and structure. Present day Māhū activists and scholars include Kahala Johnson, Kalaniopua Young, and Kumu Hina. Additional information on māhū can be found in this article by Adam Keawe Manalo-Kamp, this article by Kalani Young, and in UH system libraries (here).

Figure 17.2: Pasifika Gender Diversity: Image of the queer brown arts collective from South Auckland FAFSWAG

Figure 17.3: A photo of Robert Wadlow, the tallest person, next to his father.  https://www.flickr.com/photos/upnorthmemories/2312476677, (CC BY-NC-ND 2.0)

Robert Wadlow was the tallest person in recorded history, with a height of eight feet eleven inches. Robert had continued to grow from childhood to adulthood. Even by the time of his death, there was no indication that his growth had ended. For those who knew Robert, he was a gentle person as he was always kind to those around him. After his death, it was found that hypertrophy of the pituitary gland resulted in an abnormally high level of growth hormone (GH). From Robert’s story and his photo, we can see an example of the power of growth hormones and their effects on the body. In the human body, certain cells send chemical signals (hormones) to other cells that influence their behavior. This intercellular communication, coordination, and control are critical for homeostasis. In this chapter, we will take a closer look at the structures and functions of the endocrine system.

17.1 Regulatory Systems: The Nervous and Endocrine Systems

Have you ever wondered why it only takes a fraction of a second for you to respond to a sudden signal change when driving, but it took a few years for you to grow taller during childhood and teenage years? In the human body, two major organ systems participate in relatively “long-distance” communication: the nervous and endocrine systems. These two systems communicate by transmitting signals from the “sender” to one or more “targets” to control and coordinate actions. Together, these two systems are primarily responsible for maintaining homeostasis in the body, and they use different methods to achieve their goals.

The nervous system uses two types of intercellular communication — electrical and chemical signaling — either by the direct action of electrical potentials in electrical signaling or through the action of chemical neurotransmitters such as epinephrine in chemical signaling. Neurotransmitters act locally and rapidly. When an electrical signal in the form of an action potential arrives at the synaptic terminal, they diffuse across the synaptic cleft (the gap between a sending neuron and a receiving neuron or cell). Once the neurotransmitters interact (bind) with receptors on the receiving (postsynaptic) cell, the receptor stimulation is converted into a response such as continued electrical signaling or modification of cellular activity. The target cell responds within milliseconds of receiving the chemical “message”; this response then ceases very quickly once the neurotransmitter is removed when neural signaling ends. In this way, neural communication enables body functions that involve quick, brief actions, such as movement, sensation, and cognition.

In contrast, the endocrine system uses one primary method of communication: chemical signaling. These signals are sent by the endocrine organs, which secrete chemicals called hormones into the extracellular fluid. From here, hormones are picked up and transported primarily via the bloodstream throughout the body, where they bind to receptors on target cells to cause specific responses. As a result, endocrine signaling requires more time than neural signaling to cause a response in target cells, though the precise amount of time varies between different hormones. For example, when you are confronted with a dangerous or frightening situation (fight-or-flight response), epinephrine and norepinephrine are released within seconds by your adrenal glands. In contrast, it may take hours for target cells to respond to reproductive hormones like estradiol and progesterone, which regulate the menstrual cycle over weeks.

In general, the nervous system involves quick responses to rapid changes in the external environment, and the endocrine system is usually slower acting — taking care of the body’s internal environment, maintaining homeostasis, and controlling reproduction (Table 17.1). So how does the fight-or-flight response that was mentioned earlier happen so quickly if hormones are usually slower acting? Because the two systems are connected, the fast action of the nervous system in response to the danger in the environment stimulates the adrenal glands to secrete their hormones. As a result, the nervous system can cause rapid endocrine responses to keep up with sudden changes in both the external and internal environments when necessary.

17.2 Overview of the Endocrine System

Structure of the Endocrine System

The endocrine system consists of cells, tissues, and organs that secrete hormones as a primary or secondary function. Endocrine glands are the major player in this system. The primary function of these ductless glands is to secrete their hormones directly into the surrounding fluid. After hormones are secreted into interstitial fluid or blood, blood vessels then transport the hormones throughout the body. Examples of endocrine organs include the pituitary, thyroid, parathyroid, adrenal, and pineal glands (Figure 17.2). Other endocrine  glands may have both endocrine and nonendocrine (exocrine) functions. For example, the pancreas has exocrine functions in which pancreatic acinar cells release digestive enzymes, and endocrine functions in which pancreatic islet cells secrete hormones such as insulin and glucagon to regulate blood glucose levels. The hypothalamus, thymus, heart, kidneys, stomach, small intestine, liver, skin, female ovaries, and male testes are other organs that contain cells with endocrine functions. Moreover, adipose tissue has long been known to produce hormones, and recent research has revealed that even bone tissue and the lungs have endocrine functions.

The figure below depicts the locations of endocrine glands and cells throughout the body. The primary endocrine system organs include the hypothalamus, pituitary gland, and pineal gland, which are located in the brain. The hypothalamus is located inferior to the thalamus and the pituitary gland is inferior to the hypothalamus and located toward its anterior. The pineal gland is posterior and inferior to the thalamus. The thyroid gland is a butterfly-shaped gland that wraps around the trachea within the neck. Four small, disc-shaped parathyroid glands are embedded into the posterior side of the thyroid. The adrenal glands are located on top of the kidneys. The pancreas is located at the center of the abdomen. In females, the two ovaries are connected to the uterus by two long, curved tubes in the pelvic region. In males, the two testes are located in the scrotum below the penis.

Figure 17.4 Endocrine System Endocrine glands and cells are located throughout the body and play an essential role in homeostasis. Organs that have primary endocrine functions are displayed in this figure. (OpenStax A&P Textbook: Endocrine System)

Endocrine glands are ductless and are different from the body’s exocrine glands, which release their secretions through small tubes called ducts. Examples of exocrine glands include the sebaceous, mucous, and sudoriferous (sweat) glands of the skin. The pancreas secretes hormones as part of its endocrine function, but it also has an exocrine function where pancreatic acinar cells secrete digestive enzymes through ducts to help digest food that passes through the lumen of the small intestine.

17.3 Hormone Classes and Hormone Actions

Circulating and Local Hormones

In endocrine signaling, circulating hormones are those which are secreted into the extracellular fluid and diffuse into the blood or lymph, and they can then travel great distances throughout the body. In contrast, local hormones act on self or neighboring cells. Autocrine (auto- = self) signaling occurs when the cell secretes a hormone or molecule that causes a response in itself. For example, interleukin-1, or IL-1, is a signaling molecule that plays a primary role in the inflammatory response. Cells that secrete IL-1 have receptors on their cell surface that bind to IL-1, resulting in autocrine signaling that causes a response in the same cell that secreted IL-1. On the other hand, paracrine (para- = near) signaling occurs when the local hormones induce a response in neighboring cells. Although paracrine hormones may enter the bloodstream, their concentration is generally too low to elicit a response from distant tissues. For people with asthma, a familiar example is histamine, a paracrine hormone released by immune cells in the bronchial tree of the lungs. Histamine causes smooth muscle cells of the bronchi to constrict, thus narrowing the airways and making it harder to breathe.

Chemical Classification of Hormones

The hormones of the human body can also be divided into two major groups based on how they interact with water. Hormones derived from amino acids include amines, peptides, and proteins are water-soluble hormones. Others derived from lipids or have lipid-like characteristics are lipid-soluble hormones (Figure 17.3). These chemical classifications further relate to the hormone’s distribution in blood, the type of receptors it binds to, and how signals are relayed inside the target cells.

Water-Soluble Hormones

There are three types of water-soluble hormones: amine, peptide, and protein hormones. Whereas amine hormones are derived from a single amino acid, peptide, and protein hormones consist of multiple amino acids that link to form an amino acid chain. These water-soluble hormones are “hydrophilic” as they love interacting with water and are easily soluble in water.

Amine hormones are synthesized from amino acids. The structure of a typical amino acid has a carboxyl group and an amine group. An amine hormone is modified such that its  –COOH, or carboxyl, group is removed, whereas the −NH3+, or amine, group remains. Catecholamines such as epinephrine, norepinephrine, and dopamine, are made from the amino acid tyrosine. Epinephrine and norepinephrine are secreted by the adrenal medulla and play a role in the fight-or-flight response, whereas dopamine is secreted by the hypothalamus and inhibits the release of certain anterior pituitary hormones. Another example of an amine hormone is melatonin which is made from tryptophan and is secreted by the pineal gland to regulate your natural 24-hour daily cycle called the circadian rhythm.

On the other hand, peptide hormones consist of short chains of amino acids, whereas protein hormones are longer polypeptides. Both types are synthesized in similar ways to other body proteins: DNA is transcribed into messenger (mRNA), which is translated into an amino acid chain.

Examples of peptide hormones include oxytocin which is synthesized by the hypothalamus and released by the posterior pituitary gland. Some examples of protein hormones include growth hormone and insulin, which are produced by the pituitary gland and the pancreas, respectively. Other protein hormones, such as thyroid-stimulating hormones, have carbohydrates attached to them and they are known as glycoprotein hormones.

Figure 17.5 Amine, Peptide, Protein, and Steroid Hormone Structure. (OpenStax A&P Textbook: Endocrine System)

Figure 17.6 insulin structure (a protein hormone). By CNX OpenStax — http://cnx.org/contents/GFy_h8cu@10.53:rZudN6XP@2/Introduction, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=49923707).

Chemical Structure of Thyroid Hormone Thyroxine, also known as T4	Chemical Structure of Thyroid Hormone Triiodothyronine, also known as T3.
Chemical Structure of Nitric Oxide (NO)	Chemical Structure of Amino Acid Tyrosine

17.7 Chemical structures of thyroid hormone, NO, and tyrosine.

Lipid-Soluble Hormones

The lipid-soluble hormones include steroids, thyroid hormones, nitric oxide, and eicosanoids. Steroid hormones, or steroids, are derived from cholesterol. For example, testosterone and estrogens produced by the gonads are steroid hormones. The adrenal glands produce the steroid hormones aldosterone and cortisol, which are involved in regulating electrolyte concentrations and metabolism, respectively. Although thyroid hormones are synthesized by attaching iodine to the amino acid tyrosine, they are classified as lipid-soluble hormones. Thyroid hormones have two hexagonal benzene rings, and these structures make them very lipid-soluble. Nitric oxide (NO) is a gas, and it acts as a hormone and a neurotransmitter and plays a critical role as a vasodilator that relaxes the smooth muscle in blood vessels, causing them to widen. Eicosanoids are derived from arachidonic acid, a 20-carbon fatty acid, so they are lipid-soluble as well. Eicosanoids act more as paracrine factors and local hormones as they tend to travel limited distances in the body. Prostaglandins and leukotrienes are examples of eicosanoids that act in a variety of mechanisms, such as inflammation.

Figure 17.8: Chemical Structures of Selected Eicosanoids

Lipid-soluble hormones are hydrophobic and do not mix well with water. Since blood is water-based, lipid-soluble hormones must travel to their target cell by binding to transport proteins. This more complex hormone-transport protein structure allows steroid hormones to circulate in the body much longer than hormones derived from amino acids. A hormone’s half-life is a way of comparing how long hormones last in the body and is defined as the time required for half the concentration of the hormone to be broken down or removed from the body. For example, the lipid-soluble hormone cortisol has a half-life of approximately 60 to 90 minutes. In contrast, the water-soluble hormone epinephrine has a half-life of approximately one minute.

Mechanisms of Hormone Action

Have you ever wondered how hormones produce their actions on their target cells? Imagine that you are going home after school, and you have a specific key to your door that does not work on any other door. Hormones are similar to the key in this example. It will fit into a specific door called a hormone receptor. In cells, a hormone will bind to a specific hormone receptor, a protein located either inside the cell or embedded in the cell membrane, depending on whether the hormone is water-soluble or lipid-soluble. Hormone receptors recognize molecules with specific shapes and chemical functional groups and respond only to hormones that correctly “fit” into the receptor. Moreover, the same hormone receptor may be located on cells in different body tissues and trigger different responses in different tissues. For example, insulin stimulates glycogen synthesis when it binds to insulin receptors in liver cells but it activates fat synthesis when it binds to insulin receptors in adipose cells. Thus, the response triggered by a hormone depends not only on the hormone and receptor, but also on the target cell.

After a hormone binds to its receptor, the receptor will process the message by initiating other signaling events or mechanisms in the target cell, resulting in a hormonal response. Responses by the target cell may include stimulation of protein synthesis, activation or deactivation of enzymes, alterations in cell membrane permeability, altered rates of mitosis and cell growth, and stimulation of the secretion. Moreover, a single hormone may be capable of inducing multiple responses in a given cell. In the following section, we will look at different types of signaling mechanisms for lipid-soluble and water-soluble hormones.

Mechanism of Lipid-Soluble Hormones and Intracellular Hormone Receptors

Once lipid-soluble hormones reach their target cells, they meet and bind to their hormone receptors located in the inside of the cell. Steroid hormones are derived from cholesterol, so they can readily diffuse through the lipid bilayer of the cell membrane to reach intracellular receptors (Figure 17.9). Thyroid hormones cross the cell membrane by a specific carrier-mediated mechanism that requires both energy and Na+. Eicosanoids bind to hormone receptors located on the plasma membrane of the target cells. Researchers have been discovering membrane receptors for steroid hormones, although they are relatively recently discovered and not as well-understood as intracellular steroid hormone receptors.

We will look at the mechanism of how steroid hormones bind to their receptors. Steroid hormones travel in the blood with the help of transport proteins. Once a steroid hormone reaches a target cell, the hormone diffuses through the plasma membrane and binds to its hormone receptor within the cytosol or nucleus. In either case, this binding generates a hormone-receptor complex that binds to a particular segment of the cell’s DNA in the nucleus. The binding of the hormone-receptor complex with DNA triggers the transcription of a target gene to mRNA, which moves to the cytosol and directs protein synthesis by ribosomes.

Figure 17.9 Mechanism of Lipid-Soluble Hormones A steroid hormone directly initiates the production of proteins within a target cell. Steroid hormones easily diffuse through the cell membrane. The hormone binds to its receptor in the cytosol, forming a receptor–hormone complex. The receptor–hormone complex then enters the nucleus and binds to the target gene on the DNA. Transcription of the gene creates a messenger RNA that is translated into the desired protein within the cytoplasm. (OpenStax A&P Textbook: Endocrine System)

Mechanism of Water-Soluble Hormone and Cell Membrane Hormone Receptors

Water-soluble hormones are hydrophilic and are unable to diffuse through the lipid bilayer of the cell membrane. As a result, they must pass on their message to a receptor located at the surface of the cell. Except for lipid-soluble thyroid hormones, all amino acid-derived hormones bind to cell membrane receptors that are located, at least in part, on the extracellular surface of the cell membrane. Therefore, water-soluble hormones do not directly affect the transcription of target genes, but instead, initiate a signaling cascade that is carried out by molecules called second messengers. In this case, the hormone is called a first messenger.

The second messenger used by most hormones is cyclic adenosine monophosphate (cAMP). In the cAMP second messenger system, a water-soluble hormone binds to its receptor in the cell membrane (Step 1 in Figure 17.10). The interaction of the hormone with the receptor activates a G-protein (Step 2). The activated G protein in turn activates an enzyme called adenylyl cyclase, also known as adenylate cyclase (Step 3), which converts adenosine triphosphate (ATP) to cAMP (Step 4). The second messenger, cAMP activates a type of enzyme called a protein kinase that is present in the cytosol (Step 5). Activated protein kinases initiate phosphorylation, the addition of a phosphate group, to various cellular proteins including enzymes (Step 6).

Figure 17.10 Mechanism of Water-Soluble Hormones Water-soluble hormones cannot diffuse through the cell membrane. These hormones must bind to a surface cell-membrane receptor. The receptor then initiates a cell-signaling pathway within the cell involving G proteins, adenylyl cyclase, the secondary messenger cyclic AMP (cAMP), and protein kinases. In the final step, these protein kinases phosphorylate proteins in the cytoplasm. This activates proteins in the cell that carry out the changes specified by the hormone. (OpenStax A&P Textbook: Endocrine System)

The phosphorylation of cellular proteins can trigger a wide variety of effects including nutrient metabolism and the synthesis of different hormones and other products. The effects vary according to the type of target cell, the G proteins and kinases involved, and the phosphorylation of targeted proteins. Examples of hormones that use cAMP as a second messenger include calcitonin, which is vital for bone construction and regulating blood calcium levels; glucagon, which plays a role in blood glucose levels; and thyroid-stimulating hormone, which causes the release of T3 and T4 from the thyroid gland.

Overall, phosphorylation cascades significantly increase a hormonal response’s efficiency, speed, and specificity. Through second messenger signals and phosphorylation, thousands of signaling events can be initiated simultaneously in response to a very low hormone concentration in the bloodstream. However, the duration of the hormone signal is short, as cAMP is quickly deactivated by the enzyme phosphodiesterase (PDE), which is located in the cytosol. The action of PDE helps to ensure that a target cell’s response ceases quickly unless new hormones arrive at the cell membrane.

Regulation of Hormone Secretion

Although hormone levels can change to maintain homeostasis in the body, they must be controlled to prevent abnormal hormone levels and potential disease. The body maintains this control by balancing hormone production and degradation. There are three main ways to control hormone secretion: feedback loops, chemical changes in the blood, and signals from the nervous system.

Hormone Feedback Loops

Feedback loops are crucial for hormonal control, and this section provides an overview of common feedback loops. Positive feedback loops are characterized by the release of additional hormones in response to hormone release. An example of positive feedback is the release of oxytocin during childbirth. The initial release of oxytocin begins to signal the uterine muscles to contract, which pushes the fetus toward the cervix, causing the cervix to stretch. This stretch, in turn, signals the posterior pituitary gland to release more oxytocin, causing labor contractions to intensify. This positive feedback loop is broken after the birth of the child because the cervix is no longer stretching, thus decreasing signals to the pituitary gland, which decreases its secretion of oxytocin, which eases up on the uterine contractions.

The more common method of hormone regulation is the negative feedback loop. Negative feedback is characterized by the inhibition of further secretion of a hormone in response to adequate levels of that particular hormone. This allows blood levels of the hormone to be regulated within a normal range without resulting in an excess or lack of a hormone. An example of a negative feedback loop is the release of glucocorticoid hormones such as cortisol from the adrenal glands. The hypothalamus and pituitary gland send hormonal signals through corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH). ACTH targets the adrenal glands and stimulates the production of glucocorticoids from the adrenal cortex. As glucocorticoid concentrations in the blood rise, the hypothalamus and pituitary gland detect the increased glucocorticoids and reduce their signaling to the adrenal glands to prevent additional glucocorticoid secretion (Figure 17.11).

An endocrine gland may also secrete a hormone in response to the presence of another hormone produced by a different endocrine gland. Such hormonal stimuli often involve the hypothalamus, which produces releasing and inhibiting hormones that control the secretion of a variety of pituitary hormones.

Figure 17.11 Negative Feedback Loop The release of adrenal glucocorticoids is stimulated by the release of hormones from the hypothalamus and pituitary gland. This signaling is inhibited when glucocorticoid levels become elevated by causing negative signals to the pituitary gland and hypothalamus. (OpenStax A&P Textbook: Endocrine System)

Chemical and Neural Regulations on Endocrine Function

Besides the feedback loops, endocrine activity can also be controlled through chemical and neural regulations. Humoral (related to body fluids) stimuli are changes in blood levels of non-hormone chemicals, such as nutrients or ions. The change in the chemical composition of the blood causes the release or inhibition of a particular hormone. For example, high blood glucose levels cause the release of insulin from the pancreas. The release of insulin increases glucose uptake by cells and liver storage of glucose as glycogen. This action of insulin will cause glucose levels to decrease in the bloodstream and return it to normal homeostatic levels.

In addition to these chemical signals, hormones can also be released in response to neural stimuli. A common example of neural stimuli is the activation of the fight-or-flight response by the sympathetic nervous system. When an individual perceives danger, sympathetic neurons signal the adrenal glands to secrete epinephrine and norepinephrine to prepare the body for sudden danger. The two hormones dilate blood vessels, increase the heart and respiratory rate, and suppress the digestive, urinary, reproductive, and immune systems. These hormonal responses boost the body’s transport of oxygen to the brain and muscles, thereby improving the body’s ability to fight or flee.

17.4 Hypothalamus and Pituitary Gland

Hypothalamus

The hypothalamus and pituitary gland can be thought of as the “command center” of the endocrine system. Although the pituitary gland secretes many hormones, the hypothalamus is the primary regulator of pituitary gland activity. Together, the hypothalamus-pituitary complex secretes several hormones that directly produce responses in target tissues, as well as hormones that regulate the synthesis and secretion of hormones by other glands. These hormones play vital roles in the regulation of all body functions, ranging from homeostasis, to growth, development, and metabolism.

The hypothalamus is a structure of the diencephalon of the brain located anterior and inferior to the thalamus (Figure 17.12). It has both neural and endocrine functions where it produces and secretes many hormones. The hypothalamus is anatomically and functionally related to the pituitary gland (or hypophysis), a bean-sized organ suspended from it by a stem called the infundibulum (or pituitary stalk). The pituitary gland is cradled within the sella turcica of the sphenoid bone of the skull. It consists of two lobes that arise from distinct parts of embryonic tissue: the posterior pituitary (neurohypophysis) is neural tissue, whereas the anterior pituitary (adenohypophysis) is a glandular tissue that develops from the primitive digestive tract. The hormones secreted by the posterior and anterior pituitary glands, and the intermediate zone between the lobes are summarized in Table 17.2.

Figure 17.12 Hypothalamus–Pituitary Complex The hypothalamus region lies inferior and anterior to the thalamus. It connects to the pituitary gland by the stalk-like infundibulum. The pituitary gland consists of an anterior and posterior lobe, with each lobe secreting different hormones in response to signals from the hypothalamus. (OpenStax A&P Textbook: Endocrine System)

Table 17.2 Pituitary Hormones

Hypophyseal Portal System

Now that we understand the locations of the hypothalamus and the pituitary gland, let us look at how hypothalamic hormones reach their target cells in the pituitary gland. Near the infundibulum is a network of capillaries that connects the hypothalamus to the anterior pituitary. This network is called the hypophyseal portal system, which allows hypothalamic hormones to reach the anterior pituitary without first entering the systemic circulation. This portal system originates from the superior hypophyseal artery, which branches off the carotid arteries and transports blood to the hypothalamus (see Figure 17.13). Hypothalamic releasing and inhibiting hormones first travel through a network of small blood vessels called a primary capillary plexus to the portal veins, which then carry the hormones into the anterior pituitary. In response to the releasing hormones, the anterior pituitary produces hormones that enter a secondary capillary plexus and from there exit the anterior pituitary and enter the bloodstream that will be eventually distributed throughout the body.

Figure 17.13 Anterior Pituitary The anterior pituitary manufactures seven hormones. The hypothalamus produces separate hormones that stimulate or inhibit hormone production in the anterior pituitary. Hormones from the hypothalamus reach the anterior pituitary via the hypophyseal portal system. (OpenStax A&P Textbook: Endocrine System)

Posterior Pituitary Gland

The posterior pituitary is an extension of neurons of the paraventricular and supraoptic nuclei of the hypothalamus. The cell bodies of more than 10,000 neurons rest in the hypothalamus, but their axons descend as the hypothalamic–hypophyseal tract within the infundibulum and end in axon terminals that comprise the posterior pituitary (Figure 17.14).

Figure 17.14 Posterior Pituitary Neurosecretory cells in the hypothalamus release oxytocin (OT) and antidiuretic hormone (ADH) into the posterior lobe of the pituitary gland. These hormones are stored or released into the blood via the capillary plexus. (OpenStax A&P Textbook: Endocrine System)

The posterior pituitary gland does not produce hormones, but rather stores and secretes hormones produced by the hypothalamus. The paraventricular nuclei produce the peptide hormone oxytocin, whereas the supraoptic nuclei produce a peptide called antidiuretic hormone (ADH). These hormones travel along the axons into storage sites in the axon terminals of the posterior pituitary. In response to signals from the same hypothalamic neurons, the hormones are released from the axon terminals into the bloodstream.

Figure 17.15 Structures of Oxytocin and Antidiurectic hormone (ADH) or vasopressin (By Mauricio Aspé-Sánchez, Macarena Moreno, Maria Ignacia Rivera, Alejandra Rossi and John Ewer — Aspé-Sánchez M, Moreno M, Rivera M-I, Rossi A and Ewer J (2016) Oxytocin and Vasopressin Receptor Gene Polymorphisms: Role in Social and Psychiatric Traits. Front. Neurosci. 9:510. doi: 10.3389/fnins.2015.00510 https://www.frontiersin.org/articles/10.3389/fnins.2015.00510/full, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=72784473)

Oxytocin

Oxytocin (tocia- = childbirth) is a peptide-derived hormone that has major roles in reproduction and childbirth. When fetal development is complete, oxytocin stimulates uterine contractions and dilation of the cervix. Throughout most of pregnancy, oxytocin hormone receptors are not expressed at high levels in the uterus. Toward the end of pregnancy, the uterus increases the synthesis of oxytocin receptors, and smooth muscle cells of the uterus become more sensitive to its effects. Oxytocin is continually released throughout childbirth through a positive feedback mechanism. As noted earlier, oxytocin prompts uterine contractions that push the fetal head toward the cervix. In response, cervical stretching stimulates additional oxytocin to be synthesized by the hypothalamus and released from the posterior pituitary through the positive feedback loop system. This increases the intensity and effectiveness of uterine contractions and prompts additional stretch and dilation of the cervix. The feedback loop continues until birth.

Although a mother’s high blood levels of oxytocin begin to decrease immediately following birth, oxytocin continues to play a role in maternal and newborn health. First, oxytocin is necessary for the milk ejection reflex (commonly referred to as “let-down”) in breastfeeding females. As the newborn begins suckling, sensory receptors in the nipples transmit signals to the hypothalamus. In response, oxytocin is secreted and released into the bloodstream. Within seconds, cells in the mother’s milk ducts contract, ejecting milk into the infant’s mouth. Secondly, in both males and females, oxytocin is thought to contribute to parent–newborn bonding, known as attachment. Oxytocin is also thought to be involved in feelings of love and closeness, as well as in the sexual response.

Antidiuretic Hormone (ADH)

Solutes such as sodium ions, glucose, waste products, and other metabolites are dissolved in the blood. The solute concentration of the blood, or blood osmolarity, may change in response to the consumption of certain foods and fluids, as well as in response to disease, injury, medications, or other factors.

Blood osmolarity is constantly monitored by osmoreceptors — specialized cells within the hypothalamus that are particularly sensitive to the concentration of sodium ions and other solutes. If a situation causes blood osmolarity to be too high, for example, after eating a very salty meal, the osmoreceptors will signal the hypothalamus to release antidiuretic hormone (ADH). The kidneys are one of the primary targets of ADH. The overall effect of ADH on the kidneys is to increase epithelial permeability to water, allowing increased water reabsorption. The more water is reabsorbed in the kidneys, the greater the amount of water that is returned to the blood, resulting in less water being excreted into urine. ADH is also known as vasopressin because in very high concentrations, it causes constriction of blood vessels, which increases blood pressure by increasing peripheral resistance. In addition, ADH also decreases water loss through perspiration. Overall, the main function of ADH is to signal the body to conserve fluids. Secretion of ADH is also activated during dehydration or a loss of blood volume through volume receptors in the atria of the heart and baroreceptors in the walls of certain blood vessels.

Antidiuretic Hormone (ADH) ADH is produced in the hypothalamus and released by the posterior pituitary gland. It causes the kidneys to retain water, constricts arterioles in the peripheral circulation, and affects some social behaviors in mammals.

Aquaporins The binding of ADH to receptors on the cells of the collecting tubule results in aquaporins being inserted into the plasma membrane, shown in the lower cell. This dramatically increases the flow of water out of the tubule and into the bloodstream.

ADH and aldosterone increase blood pressure and volume. Angiotensin II stimulates release of these hormones. Angiotensin II, in turn, is formed when renin cleaves angiotensinogen. The renin-angiotensin-aldosterone system increases blood pressure and volume. The hormone ANP has antagonistic effects. (credit: modification of work by Mikael Häggström)

Figure 17.16 Function of ADH

In the absence of ADH, the amount of urine produced by your body can increase from one to two liters to about 20 liters a day. Interestingly, drugs can affect the secretion of ADH. For example, alcohol consumption inhibits ADH release, resulting in increased urine production that can eventually lead to dehydration and contributing to the symptoms of a hangover. Another situation involving abnormal levels of ADH is diabetes insipidus, a disease characterized by chronic underproduction of ADH that causes chronic dehydration. Because little ADH is produced and secreted, not enough water is reabsorbed by the kidneys. Although people with diabetes insipidus feel thirsty and increase their fluid consumption, this does not effectively decrease the solute concentration in their blood because ADH levels are not high enough to trigger water reabsorption in the kidneys. Severe cases of diabetes insipidus can result in electrolyte imbalances due to altered water and solute concentrations in the blood and body fluids. Be very aware that diabetes insipidus and diabetes mellitus are not the same and are different diseases. Diabetes insipidus involves abnormal ADH levels, whereas diabetes mellitus involves abnormal insulin levels or insulin signaling.

Anterior Pituitary Gland

The anterior pituitary originates from the digestive tract in the embryo and migrates toward the brain during fetal development. There are three regions: the pars distalis is the most anterior, the pars intermedia is adjacent to the posterior pituitary, and the pars tuberalis is a slender “tube” that wraps the infundibulum.

Recall that the posterior pituitary does not synthesize hormones, but merely stores them. In contrast, the anterior pituitary manufactures, stores, and secretes hormones. However, the secretion of hormones from the anterior pituitary is regulated by two classes of hormones. These hormones are secreted by the hypothalamus: the releasing hormones that stimulate the secretion of hormones from the anterior pituitary and the inhibiting hormones that inhibit secretion.

The anterior pituitary contains different types of endocrine cells that produce several hormones. These hormones are growth hormone (GH), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and melanocyte-stimulating hormone (MSH). MSH is produced by the pars intermedia, or intermediate zone, and is sometimes considered separate from the other anterior pituitary hormones. Of the hormones of the anterior pituitary, TSH, ACTH, FSH, and LH are collectively referred to as tropic hormones (trope- = turning) because they turn on or off the function of other endocrine glands. For example, TSH targets the thyroid gland, an endocrine gland that releases thyroid hormones.

Alternatively, trophic hormones are hormones that affect the growth, function, or nutrition of other endocrine cells. Trophic hormones can be found in body systems including the endocrine, gastrointestinal, urinary, and nervous systems. In the anterior pituitary gland, TSH is an example of a trophic hormone since it stimulates the thyroid gland to increase the size and number of cells.

Growth Hormones

In the anterior pituitary gland, somatotropic cells are responsible for secreting growth hormone, also called somatotropin. Growth hormone (GH) is a protein hormone that stimulates general body growth. GH is an anabolic hormone because its primary functions include promoting protein synthesis and tissue building through direct and indirect mechanisms (Figure 17.17). GH levels are controlled by the release of growth hormone-releasing hormone (GHRH) and growth hormone-inhibiting hormone (GHIH), also known as somatostatin, from the hypothalamus.

Figure 17.17 Hormonal Regulation of Growth Growth hormone (GH) directly accelerates the rate of protein synthesis in skeletal muscle and bones. Insulin-like growth factor 1 (IGF-1) is activated by growth hormone and indirectly supports the formation of new proteins in muscle cells and bone. (OpenStax A&P Textbook: Endocrine System)

GH indirectly mediates growth and protein synthesis by triggering the liver and other tissues to produce a group of proteins called insulin-like growth factors (IGFs). GH and IGFs proteins act as hormones where they increase numbers of cells through cellular proliferation and inhibit apoptosis or programmed cell death. The actions of GH and IGFs include the following:

1) Growth effects. In bones, IGFs stimulate osteoblasts, promote cell division at the epiphyseal plate, and enhance protein synthesis for the bone matrix. In the soft tissues, IGFs stimulate skeletal muscle cells to increase their uptake of amino acids from the blood for protein synthesis. Through IGFs, GH promotes the growth of the skeleton and soft tissues during childhood and teenage years.

2) Enhanced lipolysis. In adipose tissues, GH stimulates the breakdown of lipids into fatty acids which are used as fuels to generate ATPs for the cells.

3) Glucose-sparing effects. A glucose-sparing effect occurs when GH stimulates lipolysis or the breakdown of adipose tissue. As a result, many tissues switch from glucose to fatty acids as their primary energy source, which means that less glucose is taken up from the bloodstream.

GH also initiates the diabetogenic effect in which GH stimulates the liver to break down glycogen into glucose, which is then released into the blood. The name “diabetogenic” is derived from the similarity in elevated blood glucose levels observed between individuals with untreated diabetes mellitus and individuals experiencing GH excess. However, the causes are different. For GH, blood glucose levels rise as the result of a combination of glucose-sparing and diabetogenic effects, whereas diabetes mellitus results from problems with insulin or insulin signaling.

Dysfunction of the endocrine system’s control of growth can result in several disorders. For example, gigantism is a disorder in children that is caused by the secretion of abnormally large amounts of GH, resulting in excessive growth. A similar condition in adults is acromegaly, a disorder that results in the growth of bones in the face, hands, and feet in response to excessive levels of GH in individuals during adulthood who have stopped growing. Abnormally low levels of GH in children can cause growth impairment such as a disorder called growth hormone deficiency (also known as pituitary dwarfism)

Figure 17.18: Acromegaly. a) Photograph of the hands of a man who presented the appearances characteristic of Acromegaly

Thyroid-Stimulating Hormone (TSH)

In the anterior pituitary gland, thyrotropic cells are responsible for secreting thyroid-stimulating hormone (TSH). TSH is released in response to stimulation by thyrotropin-releasing hormone (TRH) from the hypothalamus. TSH is also called thyrotropin, and it regulates the thyroid gland to produce thyroid hormones, T3 and T4. TSH, TRH, and thyroid hormones T3 and T4 form a classic negative feedback loop in which elevated levels of thyroid hormones in the bloodstream then trigger a drop in production of TRH and subsequently TSH.

Adrenocorticotropic Hormone (ACTH)

Adrenocorticotropic hormone (ACTH), also called corticotropin, is secreted by the corticotropic cells from the anterior pituitary gland. ACTH stimulates the adrenal cortex to secrete glucocorticoids such as cortisol. The release of ACTH is stimulated by the effects of corticotropin-releasing hormone (CRH) from the hypothalamus. A variety of stressors such as low blood glucose or long-term physical stress can also influence the release of ACTH. The role of ACTH in the stress response is discussed later in this chapter.

ACTH comes from a precursor molecule known as pro-opiomelanocortin (POMC) which produces several biologically active molecules when cleaved, including ACTH, melanocyte-stimulating hormone, and the brain opioid peptides known as endorphins.

Prolactin

As its name implies, prolactin (PRL) promotes lactation (specifically milk production) in females. During pregnancy, it contributes to the development of the mammary glands. After birth, it stimulates the mammary glands to produce breast milk. However, the effects of prolactin depend heavily upon the permissive effects of estrogens, progesterone, and other hormones. As noted earlier, the let-down reflex of milk occurs in response to stimulation from oxytocin. Together, milk production and the ejection of milk through prolactin and oxytocin contribute to lactation.

In the hypothalamus, prolactin-inhibiting hormone (PIH) and prolactin-releasing hormone (PRH) regulate prolactin secretion. In a non-pregnant female, prolactin secretion is inhibited by PIH, which is purported to be the neurotransmitter dopamine. For example, before menstruation begins, PIH secretion decreases and prolactin blood levels increase. This causes breast tenderness, but there is not enough prolactin to stimulate milk production. Only during pregnancy do prolactin levels rise in response to prolactin-releasing hormone (PRH) from the hypothalamus. Prolactin is also present in males and although its effects are less studied in males than females, abnormal levels of prolactin can cause sexual dysfunction in males. A type of pituitary tumor called a prolactinoma, is an abnormal growth that results from prolactin-producing endocrine cells. This can cause galactorrhea, which is abnormal milk production outside of pregnancy, and can occur in both males and females.

Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH)

The endocrine glands secrete a variety of hormones that control the development and regulation of the reproductive system. These glands include the anterior pituitary, the adrenal cortex, and the gonads which are the ovaries in females and the testes in males. Much of the development of the reproductive system occurs during puberty and is marked by the development of sex-specific characteristics in both male and female adolescents. Puberty is initiated by gonadotropin-releasing hormone (GnRH), a hormone produced and secreted by the hypothalamus. GnRH stimulates the anterior pituitary to secrete gonadotropins which are hormones that regulate the function of the gonads.

The gonadotropins include two glycoprotein hormones: follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which work together in both the female and male reproductive systems. FSH stimulates the production and maturation of sex cells (gametes) including ova in females and sperm in males. FSH also promotes follicular growth, such as the follicles in the ovary that contain ova and release estrogens. Luteinizing hormone (LH) triggers ovulation in females, as well as the production of estrogens and progesterone by the ovaries. LH stimulates the production of testosterone by the testes. When FSH and LH levels are high enough, they will inhibit the level of GnRH through a negative feedback loop. Throughout life, gonadotropins regulate reproductive function and, in the case of females, the onset and cessation of reproductive capacity.

Melanocyte-Stimulating Hormone (MSH)

Melanocyte-stimulating hormone (MSH) is secreted by cells in the intermediate zone, or pars intermedia, located between the anterior and pituitary pituitary lobes. MSH is formed by cleavage of a larger precursor protein called pro-opiomelanocortin (POMC). Local production of MSH in the skin is responsible for melanin production in response to UV light exposure. The role of MSH made by the pituitary is more complicated. For instance, people with lighter skin generally have the same amount of MSH as people with darker skin. Nevertheless, this hormone can darken the skin by inducing melanin production in melanocytes found in the skin. Females can also show increased MSH production during pregnancy. In combination with estrogens, it can lead to darker skin pigmentation, especially the skin of the areolas and labia minora. Figure 17.19 summarizes the pituitary hormones and their principal effects.

Figure 17.19 Major Pituitary Hormones Major pituitary hormones and their target organs. Melanocyte-stimulating hormone is omitted. (OpenStax A&P Textbook: Endocrine System)

17.5 Thyroid Gland

Location and Anatomy of the Thyroid Gland

Have you ever touched and felt a butterfly-shaped soft gland near your neck? This is the thyroid gland and it is located anterior to the trachea, just inferior to the larynx (Figure 17.20). The medial region, called the isthmus, is flanked by wing-shaped left and right lobes. Each of the thyroid lobes has parathyroid glands embedded on their posterior surfaces. The tissue of the thyroid gland is composed mostly of thyroid follicles. The follicles are made up of a central cavity filled with a sticky fluid called colloid. The colloid is the center of thyroid hormone production and is contained and surrounded by a wall of epithelial follicle cells. Thyroid hormone production is dependent on thyroid hormones’ essential and unique component: iodine.

Figure 17.20 Thyroid Gland The thyroid gland is located in the neck where it wraps around the trachea. (a) Anterior view of the thyroid gland. (b) Posterior view of the thyroid gland. (c) The glandular tissue is composed primarily of thyroid follicles. The larger parafollicular cells often appear within the matrix of follicle cells. LM × 1332. (Micrograph provided by the Regents of University of Michigan Medical School © 2012) (OpenStax A&P Textbook: Endocrine System)

Synthesis and Release of Thyroid Hormones

The following steps outline how the thyroid gland assembles and makes thyroid hormones:

1. Thyroid-stimulating hormone (TSH) binding to its receptors in the follicle cells of the thyroid gland causes the cells to actively transport iodide ions (I–) across their cell membrane from the bloodstream and into their cytosol. As a result, the concentration of iodide ions “trapped” in the follicular cells is many times higher than the concentration in the bloodstream.
2. Iodide ions then move to the lumen of the follicle cells that border the colloid. There, the iodide ions (I–) undergo oxidation where their negatively charged electrons are removed. The oxidation of two iodide ions (2 I–) results in iodine (I2), which passes through the follicle cell membrane into the colloid.
3. In the colloid, peroxidase enzymes link iodine to tyrosine (an amino acid) residues in a protein called thyroglobulin, which contains many tyrosine residues. The binding of iodine to tyrosine yields two possible intermediate structures: a tyrosine attached to one iodine or a tyrosine attached to two iodines. When a tyrosine with one iodine is  covalently bonded in a correct way to a tyrosine with two iodines, the resulting compound is triiodothyronine (T3), a thyroid hormone with three iodines. More commonly, two tyrosines with two iodines each are combined to form tetraiodothyronine, also known as thyroxine (T4), a thyroid hormone with four iodines.

These hormones remain in the colloid center of the thyroid follicles until TSH stimulates endocytosis of the colloid back into the follicle cells. There, lysosomal enzymes break apart the thyroglobulin colloid, releasing free T3 and T4, which diffuse across the follicle cell membrane and enter the bloodstream.

In the bloodstream, less than one percent of the circulating T3 and T4 remain unbound. This free T3 and T4 can cross the lipid bilayer of cell membranes and be taken up by cells. The remaining 99 percent of circulating T3 and T4 is bound to specialized transport proteins called thyroxine-binding globulins (TBGs), albumin, or other plasma proteins. This “packaging” prevents their free diffusion into body cells. When blood levels of T3 and T4 begin to decline, bound T3 and T4 are released from these plasma proteins and readily cross the membrane of target cells. T3 is more potent than T4 , and many cells convert T4 to T3 through the removal of an iodine atom.

Figure 17.21 Synthesis of Thyroid Hormone. https://commons.wikimedia.org/w/index.php?curid=15534147)

Regulation of TH Synthesis

The release of T3 and T4 from the thyroid gland is regulated by thyroid-stimulating hormone (TSH) released by the pituitary gland. As shown in Figure 17.22, low blood levels of T3 and T4  stimulate the release of thyrotropin-releasing hormone (TRH) from the hypothalamus, which triggers the secretion of TSH from the anterior pituitary. In turn, TSH stimulates the thyroid gland to secrete T3 and T4  The levels of TRH, TSH, T3 and T4  are regulated by a negative feedback system in which increasing levels of T3 and T4  decrease the production and secretion of TSH and TRH.

Figure 17.22 Classic Negative Feedback Loop A classic negative feedback loop controls the regulation of thyroid hormone levels. (OpenStax A&P Textbook: Endocrine System)

Functions of Thyroid Hormones

Since most cells have thyroid hormone receptors, thyroid hormones affect tissues throughout the whole body. T3 and T4 are known as metabolic hormones where they influence the body’s overall basal metabolic rate, heat production, protein synthesis, and many other functions.

1. Increased basal metabolic rate. Thyroid hormones increase the basal metabolic rate (BMR) by raising the amount of cellular energy spent under standard conditions such as resting. When lipid-soluble T3 and T4 bind to thyroid hormone receptors located in the mitochondria, they increase the breakdown of carbohydrates, lipids, and proteins into energy. In addition, thyroid hormones also increase the numbers of enzymes involved in aerobic respiration to produce more ATP. As cells use more fuels and produce more ATP, more heat is released, and body temperature rises as a byproduct of these reactions. This calorigenic effect (calor- = heat) raises the body’s temperature. Therefore, thyroid hormones play a role in maintaining your normal body temperature.
2. Enhanced sensitivity to catecholamines. Thyroid hormones increase the body’s sensitivity to catecholamines (epinephrine and norepinephrine) by upregulation of β-adrenergic receptors. When levels of T3 and T4 hormones are excessive, catecholamines can readily bind to β-adrenergic receptors of the target cells such as the heart. For example, they accelerate the heart rate, strengthen the heartbeat, and increase blood pressure.
3. Regulating growth and development of nervous and other tissues. Adequate levels of thyroid hormones are also required for protein synthesis during fetal and childhood tissue development and growth. For instance, thyroid hormones support the synthesis of bone proteins, formation of ossification centers in developing bones, and secretion of growth hormones. Thyroid hormones are especially critical for the normal development of the nervous system both in utero and in early childhood by supporting synapse formation, myelin production, and dendrite formation. In addition, thyroid hormones continue to support neurological function in adults. As noted earlier, thyroid hormones have a complex interrelationship with reproductive hormones, and deficiencies can influence libido, fertility, and other aspects of reproductive function. Because thyroid hormones regulate metabolism, heat production, protein synthesis, and many other functions, thyroid disorders can have severe and widespread consequences.

Calcitonin

The thyroid gland also secretes a hormone called calcitonin that is produced by the parafollicular cells (also called C cells) that are located in the tissue between distinct follicles. Calcitonin is released in response to a rise in blood calcium levels. It appears to have a function in decreasing blood calcium concentrations by:

• Inhibiting the activity of osteoclasts (bone cells that release calcium into the circulation by degrading the bone matrix)
• Increasing the activity of osteoblasts
• Decreasing calcium absorption in the intestines
• Increasing calcium loss in the urine

However, recent clinical studies show that patients who had their thyroid gland removed or have deficient calcitonin levels do not show harmful effects, and abnormally high calcitonin does not seem to have harmful effects, so the importance of calcitonin is not entirely understood.

Pharmaceutical preparations of calcitonin are sometimes prescribed to reduce osteoclast activity in people with osteoporosis and to reduce the degradation of cartilage in people with osteoarthritis. Calcium is critical for many other biological processes as it is a second messenger in many signaling pathways and is essential for muscle contraction, nerve impulse transmission, and blood clotting. Given these roles, it is not surprising that blood calcium levels are tightly regulated by the endocrine system. The other glands involved in the regulation of calcium levels are the parathyroid glands.

17.6 Parathyroid Glands

The parathyroid glands are tiny, round structures embedded in the posterior surface of the thyroid gland (Figure 17.24). A thick connective tissue capsule separates the glands from the thyroid tissue. Most people have four parathyroid glands, but occasionally there are more in tissues of the neck or chest. The primary functional cells of the parathyroid glands are the chief cells. These epithelial cells produce and secrete parathyroid hormone (PTH), the major hormone involved in the regulation of blood calcium levels. The function of the other type of parathyroid cell, the oxyphil cell, is not clear.

The parathyroid glands produce and secrete PTH, a peptide hormone, in response to low blood calcium levels (Figure 17.16). PTH secretion causes the release of calcium from the bones by stimulating osteoclasts, which secrete enzymes that degrade bone and release calcium into the interstitial fluid. PTH also inhibits osteoblasts, the cells involved in bone deposition, thereby sparing blood calcium. PTH causes increased reabsorption of calcium (and magnesium) in the kidney tubules from the urine filtrate. In addition, PTH stimulates the kidneys to produce the steroid hormone calcitriol (also known as 1,25-dihydroxyvitamin D), which is the active form of vitamin D3. Calcitriol then stimulates the increased absorption of dietary calcium by the intestines. A negative feedback loop regulates the levels of PTH, with rising blood calcium levels inhibiting the further release of PTH.

Figure 17.24 Parathyroid Glands The small parathyroid glands are embedded in the posterior surface of the thyroid gland. LM × 760. (Micrograph provided by the Regents of University of Michigan Medical School © 2012) (OpenStax A&P Textbook: Endocrine System)

Endocrine Control of Blood Calcium Homeostasis

Do you remember the roles that calcium plays in the body? From the first half of this textbook, we learned how calcium plays a role in the formation of bone matrix, how it binds to troponin during muscle contraction, and how it enters the axon terminal to release neurotransmitters when conducting a nerve impulse. Calcium has a diverse role in many body functions and the level of calcium is carefully regulated in the body by parathyroid hormone (PTH) and calcitonin. When blood calcium levels are high, calcitonin is secreted, which inhibits the activity of osteoclasts and reduces the absorption of dietary calcium. On the other hand, PTH is secreted when blood calcium levels are low. PTH causes the release of calcium from the bones by stimulating osteoclasts and inhibiting osteoblasts.

Abnormally high activity of the parathyroid gland can cause hyperparathyroidism, a disorder caused by an overproduction of PTH that results in excessive calcium reabsorption from bones. Hyperparathyroidism can significantly decrease bone density, leading to spontaneous fractures or deformities. As blood calcium levels rise, cell membrane permeability to sodium is decreased, and the responsiveness of the nervous system is reduced. At the same time, calcium deposits may collect in the body’s tissues and organs, impairing their functioning.

In contrast, abnormally low blood calcium levels may be caused by a parathyroid hormone deficiency, called hypoparathyroidism, which may develop following injury or surgery involving the thyroid gland. Low blood calcium increases membrane permeability to sodium, resulting in muscle twitching, cramping, spasms, or convulsions. Severe deficits can paralyze muscles, including those involved in breathing, and can be fatal.

Figure 17.25 Parathyroid Hormone and Calcitonin in Maintaining Blood Calcium Homeostasis Parathyroid hormone increases blood calcium levels when they drop too low. Conversely, calcitonin, which is released from the thyroid gland, decreases blood calcium levels when they become too high. These two mechanisms constantly maintain blood calcium concentration at homeostasis. (OpenStax A&P Textbook: Endocrine System)

17.7 Pancreatic Islets

Let us start by saying islet correctly. Are you saying the “s”? We are living on an island in the state of Hawai‘i. If it were a very small island, we could call it an islet. The “s” is silent. And yes, you do have very small islands in your pancreas. The pancreatic islets (endocrine part of the pancreas) are surrounded by a sea of exocrine cells (digestion part of the pancreas). Figure 17.26 You may also come across the islets’ older name: islets of Langerhans. The head of the pancreas is nestled in the curve of the duodenum (first section of the small intestine). However, if the stomach were not removed from the view in this figure, the pancreas would be barely visible. To put it in a more complete perspective, imagine the pancreas with the stomach in front of it and the spine behind it.

Figure 17.26 Pancreas Pancreatic exocrine function involves the acinar cells secreting digestive enzymes that are transported into the small intestine by the pancreatic duct. Pancreatic endocrine function involves the secretion of hormones from the pancreatic islets into blood vessels. The micrograph reveals pancreatic islets. LM × 760. (Micrograph provided by the Regents of University of Michigan Medical School © 2012) (OpenStax Figure 17.18)

Interactive Link

Visit this link for an animation describing the location and function of the endocrine part of the pancreas. From what you learn in the video, what goes wrong in the function of insulin in type 2 diabetes?

Cells and Hormones of Pancreatic Islets

Within each pancreatic islet are four types of hormone-secreting cells:

• Alpha cells secrete glucagon and make up approximately 20 percent of each islet. Glucagon plays an essential role in blood glucose regulation. Low blood glucose levels stimulate the release of glucagon.
• Beta cells secrete insulin and make up approximately 70 percent of each islet. Elevated blood glucose levels stimulate the release of insulin.
• Delta cells account for seven percent of the islet cells and secrete somatostatin (growth hormone-inhibiting hormone). Somatostatin is also released by the hypothalamus, stomach, and intestines. Somatostatin inhibits the release of glucagon, insulin, and growth hormone.
• Pancreatic polypeptide cells account for about three percent of islet cells and secrete pancreatic polypeptide. This hormone is thought to play a role in appetite, as well as in the regulation of pancreatic exocrine and endocrine function. Pancreatic polypeptide released following a meal may reduce further food consumption; however, it is also released in response to fasting. In addition, it reduces gallbladder contraction.

Blood Glucose Regulation

Glucose is required for cellular respiration and is the preferred fuel for all body cells. The body obtains glucose from the breakdown of the carbohydrates found in the food and drinks we consume. Glucose not immediately taken up by cells for fuel can be stored by the liver and muscles as glycogen, or converted to fats called triglycerides and stored in adipose tissue. Hormones regulate the storage and the utilization of glucose to maintain energy homeostasis in your body. Receptors located in the pancreas sense blood glucose levels, and subsequently the pancreatic islet cells secrete glucagon or insulin to maintain normal glucose levels.

Glucagon

Receptors in the pancreas can sense the decline in blood glucose levels, such as during periods of fasting or during prolonged work or exercise. Figure 17.27 In response, the alpha cells of the pancreas secrete the hormone glucagon, which stimulates:

• Glycogenolysis — conversion and catabolism of the liver’s stored glycogen into glucose. Lysis means to break down, so glycogenolysis means to break down glycogen. The glucose is then released into the blood to provide a source of energy for the mind and body.
• Gluconeogenesis — absorption of amino acids and organic nutrients from the blood into the liver where they are converted into glucose. Let us look at the roots of this word, gluconeogenesis. (gluco- = sweet (like glucose) + neo- = new + genesis = creation) It means the creation of new glucose. Isn’t that exactly what is happening? Creating new glucose from amino acids and other sources. By thinking about the word roots, these new terms will have more meaning so you will not need to memorize something that feels like another language.
• Lipolysis — breakdown of stored triglycerides into free fatty acids and glycerol. Some of the free glycerol released into the bloodstream travels to the liver, which converts it into glucose. Recalling lysis means breakdown, lipolysis is breaking down fat. The process of converting glycerol into glucose is also a form of gluconeogenesis because that term applies to the conversion of a substance–except glycogen or monosaccharides–into glucose.

Taken together, these actions increase blood glucose levels. The activity of glucagon is regulated through a negative feedback mechanism; rising blood glucose levels inhibit further glucagon production and secretion.

Figure 17.27 Homeostatic Regulation of Blood Glucose Levels. Blood glucose concentration is maintained between 70 mg/dL and 110 mg/dL. If blood glucose concentration rises above this range, insulin is released, stimulating body cells to remove glucose from the blood. If blood glucose concentration drops below this range, glucagon is released, stimulating body cells to release glucose into the blood. (OpenStax Figure 17.19)

Insulin

The presence of food in the gastrointestinal tract triggers the release of glucose-dependent insulinotropic peptide (GIP, or formerly gastric inhibitory peptide) a hormone secreted from the small intestine. This hormone activates beta cells to increase their insulin production and secretion. Once nutrient absorption occurs (movement of food molecules from the digestive system into the blood), the resulting surge in blood glucose levels further stimulates insulin secretion. Insulin release is also triggered by meals such as loco moco because the high protein content of the hamburger and egg increase levels of the amino acids arginine and leucine in your blood. These amino acids stimulate beta cells to release insulin. The secretion of insulin is regulated through a negative feedback mechanism. As blood glucose levels decrease, further insulin release is inhibited. (Figure x.x Homeostatic Regulation of Blood Glucose Levels (see Figure 17.27 above)

Insulin lowers blood glucose by:

• Increasing facilitated diffusion of glucose into cells through recruiting glucose transporter to the plasma membrane
• Stimulating glycolysis, the metabolism of glucose for generation of ATP
• Triggering the liver to store excess glucose as glycogen (glycogenesis)
• Inhibiting enzymes involved in glycogenolysis and gluconeogenesis
• Promoting fatty acid synthesis (lipogenesis)
• Speeding cellular uptake of amino acids and protein synthesis

Red blood cells, as well as cells of the brain, liver, kidneys, and the lining of the small intestine, do not have insulin receptors on their cell membranes and do not require insulin for glucose uptake. Although all other body cells do require insulin if they are to take glucose from the bloodstream, skeletal muscle cells and adipose cells are the primary targets of insulin.

Diabetes Mellitus

In the U.S., more than one in three adults and one in six adolescents have prediabetes. Over ten percent of the U.S. population, including children, have diabetes mellitus. From 2020 to 2021, diabetes is the seventh leading cause of death in the United States because it damages blood vessels and the heart, nerves, kidneys, and other body functions. But what is diabetes mellitus? Insulin is the key factor in diabetes mellitus and problems with the body’s insulin production and secretion, as well as the target cells’ responsiveness to insulin, can lead to diabetes. Prediabetes is a condition in which blood glucose levels are abnormally high, but not yet high enough to be classified as diabetes.

There are two main types of diabetes mellitus: type 1 diabetes mellitus, and type 2 diabetes mellitus. There is another condition, diabetes insipidus, which shares part of its name with diabetes mellitus. However, diabetes insipidus is relatively uncommon compared to diabetes mellitus, so people often refer to diabetes mellitus as “diabetes” without adding mellitus. When medical professionals refer to diabetes insipidus, they make sure to include both “diabetes” and “insipidus” to avoid confusion with diabetes mellitus. Diabetes insipidus primarily involves antidiuretic hormone and is discussed in this chapter’s section on antidiuretic hormone.

The term diabetes comes from a Greek term that means siphon, as in moving fluid. In both diabetes mellitus and diabetes insipidus, people afflicted with either condition produce an excessive amount of urine, so that is why both diseases share the term “diabetes” in common. Diabetes insipidus results in the production of large volumes of dilute urine. Insipid means lacking flavor. The ancients used to taste body fluids to make a diagnosis, so with a patient who is producing (diabetes = siphon) a lot of insipid (tasteless) urine, the disorder would be diabetes insipidus. So what about diabetes mellitus? In diabetes mellitus, blood glucose is poorly controlled, causing so much glucose to build up in the blood that it eventually ends up in the urine. If the ancient healers tasted the urine, the excess glucose would have been sweet like honey. Mellitus comes from the Greek word for honey.

There are two main forms of diabetes mellitus. Type 1 diabetes (from here on, we will leave off “mellitus”) is often caused by an immune disorder, genetics, or a virus. In type 1 diabetes, the beta cells of the pancreas produce little or no insulin in response to any of those disorders. People with type 1 diabetes need synthetic insulin, which is given by injection or infusion. Type 1 diabetes is relatively rare compared to type 2 diabetes and accounts for less than five percent of all diabetes cases. Type 1 diabetes used to be called juvenile diabetes because decades ago, most patients with type 1 diabetes tended to be in their teenage years or younger, and type 2 diabetes was more common in middle-aged or older adults. However, with the diabetes epidemic and an increase in type 2 diabetes in children in recent years, “juvenile” diabetes has fallen out of favor as a name for type 1 diabetes.

Type 2 diabetes accounts for approximately 95 percent of all diabetes mellitus cases. Factors such as unhealthy diet, inactivity, obesity, and the presence of prediabetes greatly increase a person’s risk of developing type 2 diabetes. About 80 to 90 percent of people with type 2 diabetes are overweight or obese. In type 2 diabetes, the insulin receptors of the target cells become resistant to the effects of insulin. In response, the pancreas increases its insulin secretion, but over time, the beta cells become exhausted. In prediabetes or early stages of type 2 diabetes, it can be reversed by moderate weight loss, regular physical activity, and consumption of a healthy diet. However, if blood glucose levels cannot be controlled, a person with type 2 diabetes will eventually require insulin. View this video to get a better understanding of type 2 diabetes.

In both types of diabetes, the glucose level is significantly elevated to above 180 to 200 milligrams per deciliter. A constantly high blood glucose level leads to two of the early manifestations of diabetes which are excessive urination (polyuria) and excessive thirst (polydipsia). These conditions demonstrate how out-of-control levels of glucose in the blood can affect kidney function. The kidneys are responsible for maintaining water balance in your body and filtering and reabsorbing glucose from the blood. Excessive blood glucose draws water into the urine through osmosis, and as a result, the kidneys will eliminate an abnormally large quantity of urine. The use of body water to dilute the urine leaves the body dehydrated, and so a person with polyuria will be unusually and continually thirsty. The person may also experience persistent hunger (polyphagia) because the body cells are unable to access the glucose in the bloodstream.

Over time, persistently high levels of glucose in the blood injure tissues throughout the body, especially those of the blood vessels and nerves. Inflammation and injury of the lining of arteries leads to increased risks of developing cardiovascular diseases such as atherosclerosis, heart attacks, and strokes. Damage to the microscopic blood vessels of the kidney impairs kidney function and can lead to kidney failure. Damage to blood vessels that serve the eyes can lead to blindness. Blood vessel damage also reduces circulation to the limbs, whereas nerve damage leads to a loss of sensation, called neuropathy, particularly in the hands and feet. Together, these changes increase the risk of injury, infection, and tissue death, contributing to a high rate of toe, foot, and lower leg amputations in people with diabetes.

Uncontrolled diabetes can also lead to a dangerous form of metabolic acidosis called ketoacidosis. Cells that are deprived of glucose increasingly rely on fat stores for fuel. However, when the body is in a glucose-deficient state, the liver is forced to use an alternative lipid metabolism pathway that results in the increased production of acidic ketone bodies. The build-up of ketones in the blood causes an abnormally acidic condition in the body called ketoacidosis, which — if left untreated — may lead to a life-threatening diabetic coma.

Diabetes is diagnosed when lab tests reveal that blood glucose levels are consistently higher than normal, a condition called hyperglycemia, and insulin is unable to function properly in controlling hyperglycemia. The treatment of diabetes depends on the type, the severity of the condition, and the ability of the patient to make lifestyle changes. As noted earlier, moderate weight loss, regular physical activity, and consumption of a healthful diet can reduce blood glucose levels. Some patients with type 2 diabetes may be unable to control their disease with these lifestyle changes and will require medication. Historically, the first-line treatment for type 2 diabetes was insulin. Research advances have resulted in more effective options, including medications that restore the sensitivity of cells to insulin, or medications that enhance pancreatic function.

17.8 Adrenal Glands

Overview

The adrenal glands, also known as suprarenal glands, are wedge-shaped glandular and neuroendocrine tissue that adheres to the top of the kidneys by a fibrous capsule. (Figure 17.28 Adrenal Glands) The adrenal glands have a rich blood supply and experience one of the highest rates of blood flow in the body. They are served by several arteries branching off the aorta, including the suprarenal and renal arteries. Blood flows to each adrenal gland at the adrenal cortex and then drains into the adrenal medulla. Adrenal hormones are released into the circulation via the left and right suprarenal veins.

Figure 17.28 Adrenal Glands One of each of the two adrenal glands lies superior to each kidney. The adrenal glands are composed of an outer cortex and an inner medulla, all surrounded by a connective tissue capsule. The cortex is subdivided into three zones, each of which produces different hormones. LM × 204. (Micrograph provided by the Regents of University of Michigan Medical School © 2012) (OpenStax Figure 17.17)

The adrenal gland consists of the adrenal medulla, an inner region of neuroendocrine tissue, and the adrenal cortex, an outer region of glandular tissue. Each region produces different hormones.

The adrenal cortex, as a component of the hypothalamic-pituitary-adrenal (HPA) axis, secretes steroid hormones crucial for the regulation of the long-term stress response; blood pressure and blood volume; nutrient uptake and storage; fluid and electrolyte balance; and inflammation. The HPA axis begins with the hypothalamic stimulation of the pituitary to release adrenocorticotropic hormone (ACTH), which then stimulates the adrenal cortex to produce steroid hormones, most notably cortisol. This pathway will be discussed in more detail below.

The adrenal medulla is practically an extension of the autonomic nervous system, and is neuroendocrine tissue composed of modified sympathetic postganglionic neurons. The sympathomedullary (SAM) pathway stimulates the medulla by carrying nerve impulses from the hypothalamus and down along the spinal cord. These impulses emerge from the thoracic regions of the spinal cord via sympathetic preganglionic neurons which innervate and stimulate the adrenal medulla at the core of the adrenal glands. When the adrenal medulla is stimulated, it secrete the amine hormones epinephrine and norepinephrine into the blood vessels of the adrenal gland that eventually transport these hormones throughout the body.

Adrenal Response to Stress

One of the major functions of the adrenal gland is to respond to stress. Stress can be physical, psychological, or a combination of both. Examples of physical stresses include injuring a body part, standing on Mauna Kea at night without a coat, or malnutrition. Examples of psychological stresses include being threatened, having a dispute in a relationship, financial problems, or a difficult day at college.

The body responds in different ways to short-term stress and long-term stress following a pattern known as the general adaptation syndrome (GAS). Stage one of GAS is called the alarm reaction. The alarm reaction involves short-term stress initiated by the fight-or-flight response, which is caused by the release of epinephrine and norepinephrine from the adrenal medulla via the SAM pathway. The function of those hormones is to prepare the body for extreme physical exertion. Once this stress is relieved, the body quickly returns to normal. The section on the adrenal medulla covers this response in more detail.

If the initial stress is not relieved after a short time, the body adapts to the stress in the second stage called the stage of resistance, which attempts to counterbalance the changes caused by the sympathetic fight-or-flight response in the previous phase. If a person is starving, for example, the body may send signals to the gastrointestinal tract to maximize the absorption of nutrients from food. The body will also try to slow the heart rate and lower blood pressure during the stage of resistance to undo the physiological changes during the alarm reaction and restore them back to normal.

However, if the stress continues for a longer term past the stage of resistance, the body responds with symptoms quite differently than the fight-or-flight response. During the stage of exhaustion, individuals may begin to suffer depression, suppressed immune response, severe fatigue, or even a fatal heart attack. These symptoms are mediated by the hormones of the adrenal cortex, primarily cortisol, released as a result of signals from the HPA axis.

Adrenal hormones also have several non–stress-related functions, including the increase in blood sodium and glucose levels, which are described in detail below.

Adrenal Cortex

The adrenal cortex is divided into three zones: the zona glomerulosa, the zona fasciculata, and the zona reticularis. Each zone secretes its own set of hormones.

Zona Glomerulosa

The most superficial region of the adrenal cortex is the zona glomerulosa, which produces a group of steroid hormones collectively referred to as mineralocorticoids because of their effect on body minerals, especially sodium and potassium. These hormones are critical for fluid and electrolyte balance.

Aldosterone is the primary mineralocorticoid in the body. It regulates the concentration of sodium and potassium ions in urine, sweat, and saliva. For example, it is released in response to elevated blood K+, low blood Na+, low blood pressure, or low blood volume. In response, aldosterone increases the excretion of K+ and the retention of Na+ in the kidney, which in turn increases blood volume and blood pressure due to osmosis. Aldosterone secretion is stimulated when corticotropin-releasing hormone (CRH) from the hypothalamus triggers the release of adrenocorticotropic hormone (ACTH) from the anterior pituitary, which stimulates the layers of the adrenal cortex, including the zona glomerulosa that produces aldosterone.

Aldosterone is also a key component of the renin-angiotensin-aldosterone system in which specialized cells of the kidneys secrete an enzyme, renin, in response to low blood volume or low blood pressure. Renin then catalyzes the conversion of the blood protein angiotensinogen, produced by the liver, to the hormone angiotensin I. Angiotensin I is converted in the lungs to angiotensin II by angiotensin-converting enzyme (ACE). Angiotensin II has three major functions:

1. Initiating vasoconstriction of the arterioles, increasing pressure and decreasing blood flow
2. Stimulating kidney tubules to reabsorb NaCl and water, increasing blood volume
3. Signaling the adrenal cortex to secrete aldosterone, the effects of which further contribute to fluid retention, restoring blood pressure and blood volume

Individuals with high blood pressure (hypertension) may be prescribed drugs that block the production of angiotensin II in order to lower their blood pressure. Drugs that lower blood pressure are called antihypertensive drugs. ACE inhibitors are a common type of antihypertensive drug that blocks ACE from converting angiotensin I to angiotensin II. This results in lower levels of angiotensin II, which results in a lowered blood pressure.

Aldosterone also plays a role in preventing acidosis (blood pH lower than 7.35) and does this by increasing the excretion of H+ in the urine.

Zona Fasciculata

The intermediate region of the adrenal cortex is the zona fasciculata, named as such because the cells form small fascicles (bundles) separated by tiny blood vessels. The cells of the zona fasciculata produce hormones called glucocorticoids because of their role in glucose metabolism. The most abundant of these is cortisol. Cortisone and corticosterone are also glucocorticoids produced in much smaller amounts. In response to long-term stressors, the hypothalamus secretes CRH, which in turn triggers the release of ACTH by the anterior pituitary. ACTH triggers the release of glucocorticoids. The overall effect of glucocorticoids is to inhibit tissue building while stimulating the breakdown of stored nutrients to maintain adequate fuel supplies in the blood and tissues that require energy. Cortisol also has a glucose-sparing effect. For example, in long-term stress conditions, cortisol promotes the catabolism of glycogen into glucose, muscle proteins into amino acids, and stored triglycerides into fatty acids and glycerol. These raw materials can then be used to synthesize additional glucose through gluconeogenesis and also break down fatty acids into ketones for use to fuel the body with energy. There are many glucocorticoid receptors in the hippocampus found in the temporal lobe of the brain which is highly involved in memory formation. This large concentration of receptors that are impacted by sustained stress is one of the factors in stress causing difficulty in the formation of short-term and long-term memories.

You are probably familiar with prescription and over-the-counter medications containing glucocorticoids, such as cortisone injections into inflamed joints, prednisone tablets, steroid-based inhalers used to manage severe asthma, and hydrocortisone creams applied to relieve itchy rashes. These drugs reflect another role of cortisol — the downregulation of the immune system, which inhibits the inflammatory response. Cortisol’s inhibitory effects on the immune system is also why chronic stress and high levels of cortisol are linked to lower immunity and an increased risk of disease.

Zona Reticularis

The deepest region of the adrenal cortex is the zona reticularis, which produces small amounts of a class of steroid sex hormones called androgens. During puberty and most of adulthood, androgens are produced in the gonads. The androgens produced in the zona reticularis supplement the gonadal androgens. They are produced in response to ACTH from the anterior pituitary and are converted in the tissues to testosterone or estrogens. In adult females, androgens produced by the adrenal cortex may affect libido and menstrual cycles.  As the female body ages and the functions of the ovaries decline as they enter menopause, androgens produced by the zona reticularis becomes the main source of postmenopausal estrogens. The role of adrenal androgens in adult males is minimal and is relatively not well understood. Adrenal androgens only contribute less than 5% of the total testosterone in the male body, although increased levels of adrenal androgens have been linked to earlier onset of puberty in both males and females.

Adrenal Medulla

As noted earlier, the adrenal cortex releases glucocorticoids in response to long-term stress such as severe illness. In contrast, the adrenal medulla releases its hormones in response to acute, short-term stress mediated by the sympathetic nervous system (SNS).

The adrenal medulla tissue is composed of unique modified postganglionic SNS neurons called chromaffin cells, which are large and irregularly shaped and produce the neurotransmitters epinephrine (adrenaline) and norepinephrine (noradrenaline). Epinephrine is produced in greater quantities — approximately a four to one ratio with norepinephrine — and is the more powerful hormone. Once chromaffin cells release epinephrine and norepinephrine into the systemic circulation, epinephrine and norepinephrine become hormones because they can now travel widely and exert effects on distant cells and many organs. Epinephrine and norepinephrine are both derived from the amino acid tyrosine, and belong to a class of chemicals called catecholamines.

The secretion of medullary epinephrine and norepinephrine is controlled by the sympathomedullary pathway that originates from the hypothalamus in response to danger or stress. Both epinephrine and norepinephrine signal the liver and skeletal muscle cells to convert glycogen into glucose, resulting in increased blood glucose levels. These hormones increase the heart rate, pulse, and blood pressure to prepare the body to fight the perceived threat or flee from it. In addition, the sympathomedullary pathway dilates the airways, raising blood oxygen levels. It also prompts vasodilation, further increasing the oxygenation of vital organs such as the lungs, brain, heart, and skeletal muscle. At the same time, it triggers vasoconstriction to blood vessels serving fewer essential organs such as the gastrointestinal tract, kidneys, and skin, and downregulates some components of the immune system. Other effects include a dry mouth, loss of appetite, pupil dilation, and a loss of peripheral vision. This loss of peripheral vision is the “tunnel vision” experienced when we are anxious. One way to counteract that effect is to literally expand your view by looking out a window, or stepping outside if possible, and visually focusing on a distant object while feeling yourself expanding your view in each direction without much movement of the eyes. You will notice the tunnel vision, as well as the anxiety-related sensations, reduce significantly. Throw in a deep belly breath, expanding the abdomen with a deep inhalation, and you will give your body a strong signal to switch from fight-or-flight to rest-and-digest.

17.9 Pineal Gland

The pineal gland is located inferior and posterior to the thalamus, is a tiny endocrine gland that plays a role in regulating your circadian rhythm, the processes in your body that occur on an approximately 24-hour cycle. The pinealocyte cells that make up the pineal gland are known to produce and secrete the amine hormone melatonin, which is derived from serotonin, which is derived from the amino acid tryptophan.

Figure 17.29 Light and dark impact the pineal gland’s release of melatonin

The secretion of melatonin varies according to the level of light received from the environment. (Figure 17.29 Light, Suprachiasmatic nuclei (SCN), and the pinealmelatonin circuit from Wikimedia Commons) When photons of light stimulate the retinas of the eyes, a nerve impulse is sent to a region of the hypothalamus called the suprachiasmatic nucleus (SCN), which regulates biological rhythms. From the SCN, the nerve signal is carried to the spinal cord and eventually to the pineal gland, where the production of melatonin is inhibited. As a result, blood levels of melatonin fall, promoting wakefulness. In contrast, as light levels decline — such as during the evening — melatonin production increases, boosting blood levels and causing drowsiness. This entire cycle is disrupted by light from devices such as cell phones, televisions, and computers. Ideally, within a couple of hours before you want to go to sleep, keep light levels very low and avoid having light from those devices in your face. Alternatively, wearing glasses that block blue light, or changing your device screens to look nighttime mode (they will look slightly orange), can reduce the disruptive impact of blue light on your circadian rhythm. (Figure 17.30 Man Wearing White Crew-neck shirt from Unsplash)

Figure 17.30 Wearing glasses to block blue light

17.10 Reproductive Hormones

This section briefly discusses the hormonal role of the gonads — the male testes and female ovaries — which produce the sex cells (sperm and ova) and secrete the gonadal hormones. (Figure 17.31 Male Reproductive System from OpenStax) (Figure 17.32 Female Reproductive System from OpenStax) The roles of the gonadotropins released from the anterior pituitary (FSH and LH) are discussed earlier in this chapters. For further details, see the reproductive system and development chapters of this textbook.

Figure 17.31 Male Reproductive System The structures of the male reproductive system include the testes, the epididymis, the penis, and the ducts and glands that produce and carry semen. (Figure 27.2 from OpenStax)

Figure 17.32 Female Reproductive System The major organs of the female reproductive system are located inside the pelvic cavity. (Figure 27.9 from OpenStax)

The primary hormone produced by the male testes is testosterone, a steroid hormone needed in the development of the male reproductive system, the maturation of sperm cells, and the development of male secondary sex characteristics such as a deepened voice, body hair, and increased muscle mass. Interestingly, testosterone is also produced in the female ovaries, but at a much-reduced level. In addition, the testes produce the peptide hormone inhibin, which inhibits the secretion of FSH from the anterior pituitary gland. FSH stimulates spermatogenesis.

The primary hormones produced by the ovaries are estrogens, which include estradiol, estriol, and estrone. Estrogens play powerful roles in a larger number of physiological processes, including the development of the female reproductive system, regulation of the menstrual cycle, the development of female secondary sex characteristics such as increased adipose tissue, development of breast tissue, and the maintenance of pregnancy. Another significant ovarian hormone is progesterone, which contributes to the regulation of the menstrual cycle and prepares the body for pregnancy and maintaining pregnancy. Additionally, the granulosa cells of the ovarian follicles produce inhibin, which — as in males — inhibits the secretion of FSH.

During the initial stages of pregnancy, an organ called the placenta develops within the uterus. The placenta supplies oxygen and nutrients to the fetus, excretes waste products, and produces and secretes estrogens and progesterone. The placenta produces human chorionic gonadotropin (hCG) as well. The hCG hormone promotes progesterone synthesis and reduces the mother’s immune function to protect the fetus from immune rejection. It also secretes human placental lactogen (hPL), which plays a role in preparing the breasts for lactation, and relaxin, which helps soften and widen the pubic symphysis in preparation for childbirth.

17.11 Organs and Tissues with Secondary Endocrine Functions, and Paracrine Factors

In your study of anatomy and physiology, you have already encountered a few of the many organs of the body that have secondary endocrine functions. Here, you will learn about the hormone-producing activities of the heart, gastrointestinal tract, kidneys, skeleton, adipose tissue, skin, thymus, and liver.

Heart

When the body experiences an increase in blood volume or pressure, the cells of the heart’s walls also stretch. In response, specialized cells in the wall of the atria produce and secrete a peptide hormone called atrial natriuretic peptide (ANP) and cells in the walls of the ventricles produce and secrete a peptide hormone called  B-type natriuretic peptide (BNP). ANP and BNP signal the kidneys to reduce sodium reabsorption, thereby decreasing the amount of water reabsorbed from the urine filtrate and reducing blood volume. This effect is described by the term natriuretic (natrium = sodium, uresis = production of urine). Other actions of ANP and BNP include the inhibition of renin secretion, thus inhibiting the renin-angiotensin-aldosterone system, and vasodilation that widens vessels and lowers pressure. Therefore, ANP and BNP help relieve high pressures in the heart by decreasing blood pressure, blood volume, and blood sodium levels.

Gastrointestinal Tract

The endocrine cells of the gastrointestinal tract are located in the mucosa of the stomach and small intestine. Some of these hormones are secreted in response to eating a meal and aid in digestion. An example of a hormone secreted by the stomach cells is gastrin, a peptide hormone secreted in response to stomach distention that stimulates the release of hydrochloric acid. Secretin is a peptide hormone secreted by the small intestine as acidic chyme (partially digested food and fluid) moves from the stomach into the small intestine. It stimulates the release of bicarbonate from the pancreas, which buffers the acidic chyme, and inhibits the further secretion of hydrochloric acid by the stomach. Cholecystokinin is another peptide hormone released from the small intestine. It promotes the secretion of pancreatic enzymes and the release of bile from the gallbladder, both of which facilitate digestion. Other hormones produced by the intestinal cells aid in glucose metabolism, such as by stimulating the pancreatic beta cells to secrete insulin, reducing glucagon secretion from the alpha cells, or enhancing cellular insulin sensitivity.

Kidneys

The kidneys participate in several complex endocrine pathways and produce certain hormones. A decline in blood flow to the kidneys stimulates them to release the enzyme renin, triggering the renin-angiotensin-aldosterone system, and stimulating the reabsorption of sodium and water. The reabsorption increases blood flow and blood pressure. The kidneys also play a role in regulating blood calcium levels through the production of calcitriol from vitamin D3, which is released in response to the secretion of parathyroid hormone. In addition, the kidneys produce the hormone erythropoietin (EPO) in response to low oxygen levels. EPO stimulates the production of red blood cells (erythrocytes) in the bone marrow, thereby increasing oxygen delivery to tissues. You may have heard of EPO as a performance-enhancing drug (in a synthetic form) used in sports where increased oxygen delivery would benefit athletes.

Skeleton

Although bone has long been recognized as a target for hormones, only recently have researchers recognized that the skeleton itself produces at least two hormones. Fibroblast growth factor 23 is produced by bone cells in response to increased blood levels of vitamin D3 or phosphate. It triggers the kidneys to inhibit the formation of calcitriol from vitamin D3 and to increase phosphorus excretion. Osteocalcin, produced by osteoblasts, stimulates the pancreatic beta cells to increase insulin production. It also acts on peripheral tissues to increase their sensitivity to insulin and their utilization of glucose.

Adipose Tissue

Adipose tissue, commonly known as fat, produces and secretes several hormones involved in lipid metabolism and storage. One example is leptin, a protein manufactured by adipose cells and circulates in amounts directly proportional to levels of body fat. Leptin is released in response to food consumption and acts by binding to neurons in the hypothalamus that regulate energy intake and expenditure. The binding of leptin to its receptors in the brain produces a feeling of satiety after a meal, thereby reducing hunger and appetite. Have you ever noticed how after you have a poor night’s sleep, you are very hungry the next day? This is partially due to leptin levels plummeting in response to inadequate sleep. If you know someone who is trying to manage their weight, encouraging them to get good sleep may benefit them. It also appears that the binding of leptin to brain receptors triggers the sympathetic nervous system to regulate bone metabolism, increasing the deposition of cortical bone. Adiponectin — another hormone synthesized by adipose cells — appears to reduce cellular insulin resistance and protect blood vessels from inflammation and atherosclerosis. Its levels are lower in people who are obese and rise following weight loss.

Skin

The skin functions as an endocrine organ in the production of the inactive form of vitamin D3, cholecalciferol. When cholesterol present in the epidermis is exposed to ultraviolet radiation, it is converted to cholecalciferol, which then enters the blood. In the liver, cholecalciferol is converted to an intermediate that travels to the kidneys and is further converted to calcitriol, the active form of vitamin D3. Vitamin D contributes to a variety of physiological processes, including intestinal calcium absorption and immune system function. In some studies, low levels of vitamin D have been associated with increased risks of cancer, severe asthma, and multiple sclerosis. Vitamin D deficiency in children causes rickets, and in adults, osteomalacia — both of which are characterized by bone deterioration.

Thymus

The thymus is an organ of the immune system that is larger and more active during infancy and early childhood and begins to atrophy and shrink as we age. The thymus’ endocrine function is to produce a group of hormones called thymosins that contribute to the development and differentiation of a type of immune cells called T lymphocytes. Although the role of thymosins is not fully understood, it is clear that they contribute to the immune response. Thymosins have also been found in tissues other than the thymus and have a wide variety of functions, so thymosins cannot be strictly categorized as thymic hormones.

Liver

The liver is responsible for secreting several hormones or hormone precursors, including insulin-like growth factor 1 (IGF-1, also somatomedin), angiotensinogen, thrombopoietin, and hepcidin. IGF-1 is the immediate stimulus for growth in the body, especially in the bones. Angiotensinogen is the precursor to angiotensin which increases blood pressure as mentioned earlier. Thrombopoietin stimulates the production of the blood’s platelets. Hepcidins block the release of iron from cells in the body, helping to regulate iron homeostasis in our body fluids.

The major hormones of organs with secondary endocrine functions are summarized in (Table 17.3)

Paracrine and Autocrine Molecules

Prostaglandins and leukotrienes are eicosanoids, a class of molecules that serve as paracrine and autocrine hormones produced by all body cells except red blood cells. Eicosanoids are derived from arachidonic acid, and they increase or decrease the synthesis of second messengers, including cyclic AMP. Their release may be triggered by mechanical or chemical activation. Eicosanoids have a role in a variety of physiological functions, including fever, inflammation, immune function, platelet activity, and pain pathways.

Table 17.3 Organs with Secondary Endocrine Functions and Their Major Hormones (Openstax Table 17.8)

Food and Environment

Food as Hormones.

What you eat could affect your body function in a way that you may not have expected. Organic molecules like fatty acids and amino acids can stimulate or inhibit specific metabolic pathways in your cells. For example, studies have shown that omega-3 fatty acids activate a cell surface receptor called GPR120 on muscle and fat tissue cells. This could lead to improvements in metabolism, reduced inflammation, and weight loss. Other fatty acids may activate receptors that stimulate PPARgamma receptors, which is associated with increased fat intake and our urge to overeat. Amino acids can also affect metabolic pathways in our cells. For example, leucine, an amino acid, activates a network of enzymes called the mTOR pathway. Activating the mTOR pathway in hypothalamus cells results in decreased food intake and body weight. Leucine is one of the amino acids that must come from the food we eat, making it an essential amino acid (amino acids that our body can’t make). Leucine’s chemical structure contributes to its role in building and repairing muscles, some researchers say leucine may be the most important of all amino acids in this respect. Leucine is rich in salmon, chickpeas, brown rice, eggs, soybeans, and nuts. Lastly, we should also remember that microbes in our gut interact with the food we ingest. They metabolize and ferment macromolecules in the ingested food and produce short-chain fatty acids. These microbes-produced fatty acids can also change the metabolism of our body affecting how we utilize glucose and produce energy.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4240228/ (Food as a Hormone)

Salmon Poke	Omega 3 Fatty Acid Eicosapentaenoic Acid Found in Salmon	Illustration of the interaction between omega-3 fatty acids and the cardiac cell membrane (top) with the possible effect on ventricular arrhythmia (bottom)

Chapter Summary

Links and Attributions

1. Robert Wadlow (Wikipedia)
2. Chapter modified from OpenStax A&P
3. Trophic vs. non-trophic hormones (tropic vs nontropic hormones) from Wikipedia
4. Anoop TM, Jabbar PK, Pappachan JM. Lactation associated with a pituitary tumour in a man. CMAJ. 2010 Apr 6;182(6):591. doi: 10.1503/cmaj.090888. Epub 2010 Mar 1. PMID: 20194560; PMCID: PMC2845689.
5. Jameson J, & Fauci A.S., & Kasper D.L., & Hauser S.L., & Longo D.L., & Loscalzo J(Eds.), (2018). Harrison’s Principles of Internal Medicine, 20e. McGraw Hill.
6. https://www.yourhormones.info/hormones/calcitonin/
7. https://www.cdc.gov/nchs/products/databriefs/db456.htm
8. https://www.cdc.gov/diabetes/basics/what-is-type-1-diabetes.html
9. https://www.mayoclinic.org/diseases-conditions/type-1-diabetes/symptoms-causes/syc-20353011
10. Antoniou-Tsigkos A, Zapanti E, Ghizzoni L, et al. Adrenal Androgens. [Updated 2019 Jan 5]. In: Feingold KR, Anawalt B, Blackman MR, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK278929/
11. Cota D, Proulx K, Smith KA, Kozma SC, Thomas G, Woods SC, Seeley RJ. Hypothalamic mTOR signaling regulates food intake. Science. 2006 May 12;312(5775):927-30. doi: 10.1126/science.1124147. PMID: 16690869.
12. Ryan KK, Seeley RJ. Physiology. Food as a hormone. Science. 2013 Feb 22;339(6122):918-9. doi: 10.1126/science.1234062. PMID: 23430646; PMCID: PMC4240228.

Key Terms

acromegaly

disorder in adults caused when abnormally high levels of GH trigger growth of bones in the face, hands, and feet

adenylyl cyclase

membrane-bound enzyme that converts ATP to cyclic AMP, creating cAMP, as a result of G-protein activation

adiponectin

Protein hormone primarily produced by adipose (fat) tissue that reverses insulin resistance by increasing cellular insulin sensitivity, and also lowers inflammation

adrenal cortex

outer region of the adrenal glands consisting of multiple layers of epithelial cells and capillary networks that produces mineralocorticoids and glucocorticoids

adrenal glands

endocrine glands located at the top of each kidney that are important for the regulation of the stress response, blood pressure and blood volume, water homeostasis, and electrolyte levels

adrenal medulla

inner layer of the adrenal glands that plays an important role in the stress response by producing epinephrine and norepinephrine

adrenocorticotropic hormone (ACTH)

anterior pituitary hormone that stimulates the adrenal cortex to secrete corticosteroid hormones (also called corticotropin)

alarm reaction

the short-term stress, or the fight-or-flight response, of stage one of the general adaptation syndrome mediated by the hormones epinephrine and norepinephrine

aldosterone

hormone produced and secreted by the adrenal cortex that stimulates sodium and fluid retention and increases blood volume and blood pressure

alpha cell

pancreatic islet cell type that produces the hormone glucagon

amine hormones

hormones that are made from amino acids and contain a −NH3+ chemical group

Androgens

Class of sex steroid hormones that includes testosterone, primary sex hormone in males

angiotensin-converting enzyme

the enzyme that converts angiotensin I to angiotensin II

angiotensinogen

Protein secreted by the liver that is eventually converted into angiotensin II, which has more potent effects on blood pressure

anterior pituitary 

Anterior lobe of the pituitary gland that secretes hormones in response to releasing hormones from the hypothalamus (also called adenohypophysis)

antidiuretic hormone (ADH)

hypothalamic hormone that is stored by the posterior pituitary and that signals the kidneys to reabsorb water (also called vasopressin or arginine vasopressin)

atrial natriuretic peptide (ANP)

peptide hormone produced by the walls of the atria in response to high blood pressure, blood volume, or blood sodium that reduces the reabsorption of sodium and water in the kidneys and promotes vasodilation

autocrine

chemical signal that elicits a response in the same cell that secreted it

beta cell

pancreatic islet cell type that produces the hormone insulin

B-type natriuretic peptide (BNP)

peptide hormone produced by the walls of the ventricles of the heart in response to high blood pressure, blood volume, or blood sodium that reduces the reabsorption of sodium and water in the kidneys and promotes vasodilation (also called brain natriuretic peptide, although this is misleading as the heart is the main source of BNP in the human body)

calcitonin

peptide hormone produced and secreted by the parafollicular cells (C cells) of the thyroid gland that functions to decrease blood calcium levels

calcitriol 

active form of vitamin D produced by the kidneys that activates vitamin D receptors and genes controlled by those receptors

catabolism 

Breakdown of molecules into smaller molecules or energy

cholecystokinin 

peptide hormone released from the small intestine that promotes secretion of pancreatic enzymes and release of bile from the gallbladder

chromaffin

neuroendocrine cells of the adrenal medulla

circadian rhythm

Approximately 24-hour cycle of physiological changes that occur in part due to neural stimuli  daily hormonal fluctuations

circulating hormones

hormones secreted into the extracellular fluid and diffuse into the blood or lymph, where they can be carried throughout the body

colloid

viscous fluid in the central cavity of thyroid follicles, containing the glycoprotein thyroglobulin

cortisol

glucocorticoid important in gluconeogenesis, the catabolism of glycogen, and downregulation of the immune system

cyclic adenosine monophosphate (cAMP)

second messenger that, in response to adenylyl cyclase activation, triggers a phosphorylation cascade

delta cell

minor cell type in the pancreas that secretes the hormone somatostatin

diabetes mellitus

condition caused by destruction or dysfunction of the beta cells of the pancreas or cellular resistance to insulin that results in abnormally high blood glucose levels

diabetogenic effect

Elevated blood glucose levels caused by a conditon

eicosanoid

Type of lipid-derived molecule derived from arachadonic acid that acts primarily as paracrine factors

endocrine gland

tissue or organ that secretes hormones into the blood and lymph without ducts such that they may be transported to organs distant from the site of secretion

endocrine system

cells, tissues, and organs that secrete hormones as a primary or secondary function and play an integral role in normal bodily processes

epinephrine

primary and most potent catecholamine hormone secreted by the adrenal medulla in response to short-term stress; also called adrenaline

erythropoietin (EPO)

protein hormone secreted in response to low oxygen levels that triggers the bone marrow to produce red blood cells

estrogens

class of predominantly female sex hormones important for the development and growth of the female reproductive tract, secondary sex characteristics, the female reproductive cycle, and the maintenance of pregnancy

fibroblast growth factor 23 (FGF23)

Protein hormone produced by osteocytes that responds to increased blood levels of vitamin D3 or phosphate and functions to increase phosphorus excretion and decrease calcitriol synthesis

first messenger

hormone that binds to a cell membrane hormone receptor and triggers activation of a second messenger system

follicle-stimulating hormone (FSH)

anterior pituitary hormone that stimulates the production and maturation of sex cells

G protein

protein associated with a cell membrane hormone receptor that initiates the next step in a second messenger system upon activation by hormone–receptor binding

gastrin

peptide hormone secreted in response to stomach distention that stimulates the release of hydrochloric acid

general adaptation syndrome (GAS)

the human body’s three-stage response pattern to short- and long-term stress

gigantism

disorder in children caused when abnormally high levels of GH prompt excessive growth

glucagon

pancreatic hormone that stimulates the catabolism of glycogen to glucose, thereby increasing blood glucose levels

glucocorticoids

hormones produced by the zona fasciculata of the adrenal cortex that influence glucose metabolism

Gluconeogenesis 

Conversion of organic nutrients into newly synthesized glucose

glucose-dependent insulinotropic peptide (GIP)

(formerly gastric inhibitory peptide) hormone secreted by the small intestine that stimulates increased insulin secretion

Glycogenolysis

Process of catabolizing and converting stored glycogen into glucose

goiter

enlargement of the thyroid gland either as a result of iodine deficiency or hyperthyroidism

Gonad

Reproductive organ (ovary in females, testis in males) that produces sex cells (ovum in females, sperm in males)

gonadotropin-releasing hormone (GnRH)

hormone produced and secreted by the hypothalamus that stimulates production of gonadotropins

gonadotropins

hormones that regulate the function of the gonads, namely follicle-stimulating hormone (FSH) and luteinizing hormone (LH)

Graves’ disease

Condition where an autoimmune reaction produces antibodies that act like TSH and cause overproduction of thyroid hormones leading to hyperthyroidism

growth hormone (GH)

anterior pituitary hormone that promotes tissue building and influences nutrient metabolism (also called somatotropin)

growth hormone deficiency (GHD)

disorder in children caused when abnormally low levels of GH result in delayed growth and short stature (also called pituitary dwarfism)

growth hormone-releasing hormone (GHRH)

Hormone secreted by the hypothalamus that triggers the release of growth hormone from the anterior pituitary

growth hormone-inhibiting hormone (GHIH)

Inhibitory hormone that inhibits the release of growth hormone and other hormones, including thyroid-stimulating hormone and prolactin (also called somatostatin)

hepcidin

Hormone secreted by the liver that regulates iron levels in blood plasma by blocking the release of iron from cells into the plasma and reducing dietary absorption of iron 

hormone

secretion of an endocrine organ that travels via the bloodstream or lymphatics to induce a response in target cells or tissues in another part of the body

hormone receptor

protein within a cell or on the cell membrane that binds a hormone, initiating the target cell response

hormone-receptor complex

Structure formed when a hormone binds to its hormone receptor

human chorionic gonadotropin (hCG)

Hormone produced by the placenta that promotes progesterone synthesis and reduces the mother’s immune function to protect the fetus from immune rejection.

human placental lactogen (hPL)

Hormone produced by the placenta that prepares mammary glands for lactation

humoral

Related to body fluids

hyperglycemia

abnormally high blood glucose levels

hyperparathyroidism

disorder caused by overproduction of PTH that results in abnormally elevated blood calcium

hyperthyroidism

clinically abnormal, elevated level of thyroid hormone in the blood; characterized by an increased metabolic rate, excess body heat, sweating, diarrhea, weight loss, and increased heart rate

hypoparathyroidism

disorder caused by underproduction of PTH that results in abnormally low blood calcium

hypophyseal portal system

network of blood vessels that enables hypothalamic hormones to travel into the anterior lobe of the pituitary without entering the systemic circulation

hypothalamic-pituitary-adrenal (HPA) axis

Endocrine control system involving the hypothalamus, pituitary gland, and adrenal cortex, the hormones secreted by those glands, and regulation of adrenal cortex steroid production by those hormones

hypothalamus

region of the diencephalon inferior to the thalamus that functions in neural and endocrine signaling

hypothyroidism

clinically abnormal, low level of thyroid hormone in the blood; characterized by low metabolic rate, weight gain, cold extremities, constipation, and reduced mental activity

infundibulum

stalk containing vasculature and neural tissue that connects the pituitary gland to the hypothalamus (also called the pituitary stalk)

inhibin

hormone secreted by the male and female gonads that inhibits FSH production by the anterior pituitary

inhibiting hormone

Hormone that prevents or decrease the release of other hormones

insulin

pancreatic hormone that enhances the cellular uptake and utilization of glucose, thereby decreasing blood glucose levels

insulin-like growth factor 1 (IGF-1)

protein that enhances cellular proliferation, inhibits apoptosis, and stimulates the cellular uptake of amino acids for protein synthesis (also, somatomedin)

Ketoacidosis

Abnormally high levels of acid in the blood caused by increased levels of ketone bodies leptin

protein hormone secreted by adipose tissues in response to food consumption that promotes satiety

lipid-soluble hormones

hydrophobic hormones that easily dissolve in fats and oils, and tend to dissolve poorly in water-based fluids

Lipolysis 

Catabolism of triglycerides into free fatty acids and glycerol

local hormones

hormones that act upon neighboring cells or the original cell that secreted them

luteinizing hormone (LH)

anterior pituitary hormone that triggers ovulation and the production of ovarian hormones, and the production of testosterone

Melanocyte-stimulating hormone

Hormone secreted by the intermediate zone of the pituitary gland that increase melanocyte production of melanin

melatonin

amino acid–derived hormone that is secreted in response to low light and causes drowsiness

milk ejection reflex

Process occurring in breastfeeding where an infant’s suckling triggers the movement of milk from breast alveoli to milk ducts that eject milk into the infant’s mouth (also called let-down reflex) 

mineralocorticoids

hormones produced by the zona glomerulosa cells of the adrenal cortex that influence fluid and electrolyte balance

negative feedback

In the endocrine system, a situation in which an initial change triggers the release of a hormone that lessens or returns the initial change back to its normal or starting state

neonatal hypothyroidism

Thyroid hormone deficiency present at birth and can result in problems with physical and intellectual growth and development (also congenital hypothyroidism, cretinism (outdated))

nitric oxide (NO)

gas that can act as a neurotransmitter, paracrine factor, and hormone

norepinephrine

secondary catecholamine hormone secreted by the adrenal medulla in response to short-term stress; also called noradrenaline

osmoreceptor

hypothalamic sensory receptor that is stimulated by changes in solute concentration (osmotic pressure) in the blood

osteocalcin

Hormone produced by osteoblasts that stimulates the pancreas to increase insulin production

oxytocin

hypothalamic hormone stored in the posterior pituitary gland and important in stimulating uterine contractions in labor, milk ejection during breastfeeding, and feelings of attachment (produced by males and females)

pancreas

organ with both exocrine and endocrine functions located posterior to the stomach that is important for digestion and the regulation of blood glucose

pancreatic islets

specialized clusters of pancreatic cells that have endocrine functions; also called islets of Langerhans

Pancreatic polypeptide cells

(formerly gamma cells or F cells) Cells in pancreatic islets that secrete pancreatic polypeptide 

paracrine

chemical signal that elicits a response in neighboring cells; also called paracrine factor

parathyroid glands

small, round glands embedded in the posterior thyroid gland that produce parathyroid hormone (PTH)

parathyroid hormone (PTH)

peptide hormone produced and secreted by the parathyroid glands in response to low blood calcium levels

peptide hormone

Hormone that is made from a relatively short polypeptide chain made out of amino acids

phosphodiesterase (PDE)

cytosolic enzyme that deactivates and degrades cAMP

phosphorylation cascade

signaling event in which multiple protein kinases phosphorylate the next protein substrate by transferring a phosphate group from ATP to the protein

pineal gland

endocrine gland that secretes melatonin, which is important in regulating the sleep-wake cycle

pinealocyte

cell of the pineal gland that produces and secretes the hormone melatonin

pituitary gland

bean-sized organ suspended from the hypothalamus that produces, stores, and secretes hormones in response to hypothalamic stimulation (also called hypophysis)

positive feedback

In the endocrine system, a situation in which a stimulus or change triggers the release of a hormone, which increases and exaggerates the change, eventually resulting in amplification of the initial change and hormone levels

posterior pituitary 

Posterior portion of the pituitary gland made up of neural tissue (also called neurohypophysis)

protein hormone

Hormone that is made from a longer polypeptide chain as compared to relatively shorter peptide hormones

progesterone

predominantly female sex hormone important in regulating the female reproductive cycle and the maintenance of pregnancy

prolactin (PRL)

anterior pituitary hormone that promotes development of the mammary glands and the production of breast milk

protein kinase

enzyme that initiates a phosphorylation cascade upon activation

relaxin

Hormone produced by the placenta and ovaries that softens the fibrocartilage of the pubic symphysis, allowing it and the pelvic girdle to widen for childbirth

releasing hormone

Hormone secreted by the hypothalamus that targets endocrine cells in the anterior pituitary, which secretes a different hormone in response

renin-angiotensin-aldosterone system

Endocrine control system involving hormones such as angiotensin II and aldosterone that work together to increase blood pressure and volume

second messenger

molecule that initiates a signaling cascade in response to hormone binding on a cell membrane receptor and activation of a G protein

secretin 

peptide hormone that stimulates the release of bicarbonate from the pancreas

somatostatin

Inhibitory hormone that inhibits the release multiple hormones, including growth hormone, thyroid-stimulating hormone, and prolactin (also called growth hormone-inhibiting hormone)

stage of exhaustion

stage three of the general adaptation syndrome; the body’s long-term response to stress mediated by the hormones of the adrenal cortex

stage of resistance

stage two of the general adaptation syndrome; the body’s continued response to stress after stage one diminishes

Steroid hormone

hormone that is originally made from cholesterol and tends to be lipid-soluble and dissolves poorly in water

sympathomedullary (SAM) pathway

Pathway by which nerve impulses travel along sympathetic nerve fibers from the hypothalamus and eventually to the adrenal medulla

testosterone

steroid hormone secreted by the testes and important in the maturation of sperm cells, growth and development of the reproductive system, and the development of secondary sex characteristics

thrombopoietin

Hormone produced by the liver that stimulates platelet production

thymosins

hormones produced and secreted by the thymus that play an important role in the development and differentiation of T cells

thymus

organ that is involved in the development and maturation of T-cells and is particularly active during infancy and childhood

thyroid gland

large endocrine gland responsible for the synthesis of thyroid hormones

thyroid-stimulating hormone (TSH)

anterior pituitary hormone that triggers secretion of thyroid hormones by the thyroid gland (also called thyrotropin)

thyroxine

(also, tetraiodothyronine, T4) amino acid–derived thyroid hormone that is more abundant but less potent than T3 and often converted to T3 by target cells

thyrotropin-releasing hormone (TRH)

Hormone secreted by the hypothalamus that stimulates the pituitary gland to secrete thyroid-stimulating hormone

triiodothyronine

(also, T3) amino acid–derived thyroid hormone that is less abundant but more potent than T4

trophic hormone

hormones that affect the growth, function, or nutrition of other endocrine cells

tropic hormone

Hormone that stimulates or inhibits the function of other endocrine glands

tyrosine 

Amino acid used in the synthesis of hormones like catecholamines and thyroid hormones

water-soluble hormones

hydrophilic hormones that easily dissolve in water

zona fasciculata

intermediate region of the adrenal cortex that produce hormones called glucocorticoids

zona glomerulosa

most superficial region of the adrenal cortex, which produces the hormones collectively referred to as mineralocorticoids

zona reticularis

deepest region of the adrenal cortex, which produces the steroid sex hormones called androgens