17 Endocrine System

Oxytocin

When fetal development is complete, the peptide-derived hormone oxytocin (tocia- = “childbirth”) 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 synthesis of oxytocin receptors in the uterus increases, and the 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 pituitary. This increases the intensity and effectiveness of uterine contractions and prompts additional dilation of the cervix. The feedback loop continues until birth.

Although the 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 women. 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)

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.

In response to high blood osmolarity, which can occur during dehydration or following a very salty meal, the osmoreceptors signal the posterior pituitary to release antidiuretic hormone (ADH). The target cells of ADH are located in the tubular cells of the kidneys. Its effect is to increase epithelial permeability to water, allowing increased water reabsorption. The more water reabsorbed from the filtrate, the greater the amount of water that is returned to the blood and the less that is excreted in the urine. A greater concentration of water results in a reduced concentration of solutes. 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. The release of ADH is controlled by a negative feedback loop. As blood osmolarity decreases, the hypothalamic osmoreceptors sense the change and prompt a corresponding decrease in the secretion of ADH. As a result, less water is reabsorbed from the urine filtrate.

Interestingly, drugs can affect the secretion of ADH. For example, alcohol consumption inhibits the release of ADH, resulting in increased urine production that can eventually lead to dehydration and a hangover. A disease called diabetes insipidus is 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 patients feel thirsty, and increase their fluid consumption, this doesn’t effectively decrease the solute concentration in their blood because ADH levels are not high enough to trigger water reabsorption in the kidneys. Electrolyte imbalances can occur in severe cases of diabetes insipidus.

Follicle-Stimulating Hormone and Luteinizing Hormone

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—the testes in males and the ovaries in females). 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—hormones that regulate the function of the gonads. The levels of GnRH are regulated through a negative feedback loop; high levels of reproductive hormones inhibit the release of GnRH. Throughout life, gonadotropins regulate reproductive function and, in the case of women, the onset and cessation of reproductive capacity.

The gonadotropins include two glycoprotein hormones: follicle-stimulating hormone (FSH) stimulates the production and maturation of sex cells, or gametes, including ova in women and sperm in men. FSH also promotes follicular growth; these follicles then release estrogens in the female ovaries. Luteinizing hormone (LH) triggers ovulation in women, as well as the production of estrogens and progesterone by the ovaries. LH stimulates production of testosterone by the male testes.

Prolactin

As its name implies, prolactin (PRL) promotes lactation (milk production) in women. During pregnancy, it contributes to development of the mammary glands, and 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. And as noted earlier, the let-down of milk occurs in response to stimulation from oxytocin.

In a non-pregnant woman, prolactin secretion is inhibited by prolactin-inhibiting hormone (PIH), which is actually the neurotransmitter dopamine, and is released from neurons in the hypothalamus. Only during pregnancy do prolactin levels rise in response to prolactin-releasing hormone (PRH) from the hypothalamus.

Aldosterone is also a key component of the renin-angiotensin-aldosterone system (RAAS) in which specialized cells of the kidneys secrete the 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, 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

For individuals with hypertension, or high blood pressure, drugs are available that block the production of angiotensin II. These drugs, known as ACE inhibitors, block the ACE enzyme from converting angiotensin I to angiotensin II, thus mitigating the latter’s ability to increase blood pressure.

Glucocorticoid

The glucocorticoid hormones play a role in glucose metabolism. The most important of these is cortisol, some of which the liver converts to cortisone. A glucocorticoid produced in much smaller amounts is corticosterone. 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 the glucocorticoids. Their overall effect is to inhibit tissue building while stimulating the breakdown of stored nutrients to maintain adequate fuel supplies. In conditions of long-term stress, for example, cortisol promotes the catabolism of glycogen to glucose, the catabolism of stored triglycerides into fatty acids and glycerol, and the catabolism of muscle proteins into amino acids. These raw materials can then be used to synthesize additional glucose and ketones for use as body fuels. The hippocampus, which is part of the temporal lobe of the cerebral cortex and important in memory formation, is highly sensitive to stress levels because of its many glucocorticoid receptors.

You are probably familiar with prescription and over-the-counter medications containing glucocorticoids, such as cortisone injections into inflamed joints, prednisone tablets and steroid-based inhalers used to manage severe asthma, and hydrocortisone creams applied to relieve itchy skin rashes. These drugs reflect another role of cortisol—the downregulation of the immune system, which inhibits the inflammatory response.

Androgens

The deepest region of the adrenal cortex 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 women, they may contribute to the sex drive, but their function in adult men is not well understood. In post-menopausal women, as the functions of the ovaries decline, the main source of estrogens becomes the androgens produced by the zona reticularis.

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 medullary tissue is composed of unique postganglionic SNS neurons called chromaffin cells, which are large and irregularly shaped, and produce the neurotransmitters epinephrine (also called adrenaline) and norepinephrine (or noradrenaline). Epinephrine is produced in greater quantities—approximately a 4 to 1 ratio with norepinephrine—and is the more powerful hormone. Because the chromaffin cells release epinephrine and norepinephrine into the systemic circulation, where they travel widely and exert effects on distant cells, they are considered hormones. Derived from the amino acid tyrosine, they are chemically classified as catecholamines.

The secretion of medullary epinephrine and norepinephrine is controlled by a neural 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 pathway dilates the airways, raising blood oxygen levels. It also prompts vasodilation, further increasing the oxygenation of important organs such as the lungs, brain, heart, and skeletal muscle. At the same time, it triggers vasoconstriction to blood vessels serving less 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.

Pancreas

The pancreas is a long, slender organ, most of which is located posterior to the bottom half of the stomach (see Figure 17.7). Although it is primarily an exocrine gland, secreting a variety of digestive enzymes, the pancreas has an endocrine function. Its pancreatic islets—clusters of cells formerly known as the islets of Langerhans—secrete the hormones glucagon, insulin, somatostatin, and pancreatic polypeptide (PP).

 

Cells and Secretions of the Pancreatic Islets

The pancreatic islets each contain four varieties of cells:

• The alpha cell produces the hormone glucagon and makes up approximately 20 percent of each islet. Glucagon plays an important role in blood glucose regulation; low blood glucose levels stimulate its release.
• The beta cell produces the hormone insulin and makes up approximately 75 percent of each islet. Elevated blood glucose levels stimulate the release of insulin.
• The delta cell accounts for four percent of the islet cells and secretes the peptide hormone somatostatin. Recall that somatostatin is also released by the hypothalamus (as GHIH), and the stomach and intestines also secrete it. An inhibiting hormone, pancreatic somatostatin inhibits the release of both glucagon and insulin.
• The PP cell accounts for about one percent of islet cells and secretes the pancreatic polypeptide hormone. It is thought to play a role in appetite, as well as in the regulation of pancreatic exocrine and endocrine secretions. Pancreatic polypeptide released following a meal may reduce further food consumption; however, it is also released in response to fasting.

Regulation of Blood Glucose Levels by Insulin and Glucagon

Glucose is required for cellular respiration and is the preferred fuel for all body cells. The body derives glucose from the breakdown of the carbohydrate-containing foods 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 triglycerides and stored in the adipose tissue. Hormones regulate both the storage and the utilization of glucose as required. Receptors located in the pancreas sense blood glucose levels, and subsequently the pancreatic cells secrete glucagon or insulin to maintain normal levels.

Gonadal Glands

The male testes and female ovaries—which produce the sex cells (sperm and ova) and secrete the gonadal hormones. The roles of the gonadotropins released from the anterior pituitary (FSH and LH) were discussed earlier.

The primary hormone produced by the male testes is testosterone, a steroid hormone important 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 an important role 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 and the development of breast tissue, and the maintenance of pregnancy. Another significant ovarian hormone is progesterone, which contributes to regulation of the menstrual cycle and is important in preparing the body for pregnancy as well as maintaining pregnancy. In addition, 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 is thought to help soften and widen the pubic symphysis in preparation for childbirth.