Endocrine System

History of endocrinology

Basic endocrine principles

The pituitary

The pineal

The thyroid

The parathyroids

The thymus

The pancreas

The adrenals

The ovaries

The testes

Endocrine disorders

Resources

The endocrine system is the human body’s group of specialized organs and tissues that produce, store, and secrete chemical hormones. This network of nine glands and over 100 hormones that maintain and regulate numerous events throughout the body. The glands of the endocrine system include the pituitary, thyroid, parathyroids, thymus, pancreas, pineal, adrenals, and ovaries or testes: in addition, the hypothalamus, in the brain, regulates the release of pituitary hormones. Each of these glands secrete hormones (chemical messengers) into the blood stream. Once hormones enter the blood, they travel throughout the body and are detected by receptors that recognize

specific hormones. These receptors exist on target cells and organs. Once a target site is bound by a particular hormone, a cascade of cellular events follows that culminates in the physiological response to a particular hormone.

The endocrine system differs from the exocrine system in that exocrine glands contain ducts that direct their hormones to specific sites; whereas endocrine hormones travel through blood until they reach their destination. The endocrine is also similar to the nervous system, because both systems regulate body events and communicate through chemical messengers with target cells. However, the nervous system transmits neurotransmitters (also chemical messengers) between neighboring neurons via nerve extension, and neurotransmitters do not generally enter the circulation. Yet, some overlap between hormones and neurotransmitters exists, which gives rise to chemical signals called neurohormones that function as part of the neuroendocrine system. The endocrine system oversees many critical life processes involving metabolism, growth, reproduction, immunity, and homeostasis. The branch of medicine that studies endocrine glands and the hormones that they secrete is called endocrinology.

History of endocrinology

Although some ancient cultures noted biological observations grounded in endocrine function, modern understanding of endocrine glands and how they secrete hormones has evolved only in the last 300 years. Ancient Egyptian and Chinese civilizations castrated (removed the testicles of) a servile class of men called eunuchs. It was noted that eunuchs were less aggressive than other men, but the link of this behavior to testosterone was not made until recently.

Light was shed on endocrine function during the seventeenth and eighteenth centuries by a few significant advances. Seventeenth century English scientist, Thomas Wharton (1614–1673) noted the distinction between ductile and ductless glands. In the 1690s, Dutch scientist Fredrik Ruysch (1638–1731) first stated that the thyroid secreted important substances into the blood stream. A few decades later, Theophile Bordeu (1722–1776) claimed that “emanations” were given off by some body parts that influenced functions of other body parts.

One of the greatest early experiments performed in endocrinology was published by A. A. Berthold (1803–1861) in 1849. Berthold took six young male chickens, and castrated four of them. The other two chickens were left to develop normally; thus, they were used comparatively as control samples. Two of the castrated chickens were left to become chicken eunuchs. However, what Berthold did with the other two castrated chickens is what really changed endocrinology. He transplanted the testes back into these two chickens at a distant site from where they were originally. The two castrated chickens never matured into roosters with adult combs or feathers. However, the chickens that received transplanted testes did mature into normal adult roosters. This experiment revealed that hormones that could access the blood stream from any site would function correctly in the body and that hormones did, in fact, travel freely in the circulation.

The same year Berthold published his findings, Thomas Addison (1793–1860), a British scientist, reported one of the first well documented endocrine diseases which was later named Addison’s disease (AD). AD patients all had a gray complexion with sickly skin; they also had weak hearts and insufficient blood levels of hemoglobin necessary for oxygen transport throughout the body. On autopsy, each of the patients Addison studied was found to have diseased adrenal glands. This disease can be controlled today if it is detected early. President John F. Kennedy (1917–1963) suffered from AD.

Basic endocrine principles

Most endocrine hormones are maintained at specific concentrations in the plasma, the non-cellular, liquid portion of the blood. Receptors at set locations monitor plasma hormonal levels and inform the gland responsible for producing that hormone if levels are too high or too low for a particular time of day, month, or other life period. When excess hormone is present, a negative feedback loop is initiated such that further hormone production is inhibited. Most hormones have this type of regulatory control. However, a few hormones operate on a positive feedback cycle such that high levels of the particular hormone will activate release of another hormone. With this type of feedback loop, the end result is usually that the second hormone released will eventually decrease the initial hormone’s secretion. An example of positive feedback regulation occurs in the female menstrual cycle, where high levels of estrogen stimulate release of the pituitary hormone, luteinizing hormone (LH).

All hormones are influenced by numerous factors. The hypothalamus can release inhibitory or stimulatory hormones that determine pituitary function. In addition, every physiological component that enters the circulation can affect some endocrine function. Overall, this system uses multiple bits of chemical information to hormonally maintain a biochemically balanced organism.

Endocrine hormones do not fall into any one chemical class, but most are either a protein (polypep-tides, peptides, and glycoproteins are also included in this category) or a steroid. Protein hormones bind cell-surface receptors and activate intracellular events that carry out the hormone’s response. Steroid hormones, on the other hand, usually travel directly into the cell and bind a receptor in the cell’s cytoplasm or nucleus. From there, steroid hormones (bound to their receptors) interact directly with genes in the DNA (deoxy-ribonucleic acid) to elicit a hormonal response.

The pituitary

The pituitary gland has long been called the master gland, because it secretes multiple hormones that, in turn, trigger the release of other hormones from other endocrine sites. The pituitary is roughly situated behind the nose and is anatomically separated into two distinct lobes, the anterior pituitary (AP) and the posterior pituitary (PP). The entire pituitary hangs by a thin piece of tissue, called the pituitary stalk, beneath the hypothalamus in the brain. The AP and PP are sometimes called the adenohypophysis and neurohypophysis, respectively.

The PP secretes two hormones, oxytocin and anti-diuretic hormone (ADH), under direction from the hypothalamus. Direct innervation of the PP occurs from regions of the hypothalamus called the supraoptic and paraventricular nuclei. Although the PP secretes its hormones into the bloodstream through blood vessels that supply it, it is regulated in a neuroendocrine fashion. The AP, on the other hand, receives hormonal signals from the blood supply within the pituitary stalk.

AP cells are categorized according to the hormones that they secrete. The hormone-producing cells of the AP include: somatotrophs, corticotrophs, thyrotrophs, lactotrophs, and gonadotrophs. Somatotrophs secrete growth hormone; corticotrophs secrete adrenocortico-tropic hormone (ACTH); thyrotrophs secrete thyroid stimulating hormone (TSH); lactotrophs secrete prolactin; and gonadotrophs secrete LH and follicle stimulatory hormone (FSH). Each of these hormones sequentially signals a response at a target site. While ACTH, TSH, LH, and FSH primarily stimulate other major endocrine glands, growth hormone and prolactin primarily coordinate an endocrine response directly on bones and mammary tissue, respectively.

The pineal

The pineal gland is a small cone-shaped gland believed to function as a body clock. The pineal is located deep in the brain just below the rear-most portion of the corpus callosum (a thick stretch of nerves that connects the two sides of the brain). The pineal gland, also called the pineal body, has mystified scientists for centuries. Seventeenth century French mathematician and philosopher Rene´ Descartes (1596–1650) speculated that the pineal was the seat of the soul. However, its real function is somewhat less grandiose than that described by Descartes.

The pineal secretes the hormone melatonin, which fluctuates on a daily basis with levels highest at night. Although its role is not well understood, some scientists believe that melatonin helps to regulate other diurnal events, because melatonin fluctuates in a 24-hour period. Exactly what controls melatonin levels is not well understood either; however, visual registration of light may regulate the cycle.

The thyroid

The thyroid is a butterfly-shaped gland that wraps around the back of the esophagus. The two lobes of the thyroid are connected by a band of tissue called the isthmus. An external covering of connective tissue separates each lobe into another 20 to 40 follicles. Between the follicles are numerous blood and lymph vessels in another connective tissue called stroma. The epithelial cells around the edge of the follicles produce the major thyroid hormones.

The major hormones produced by the thyroid are triiodothyronine (T3), thyroxine(T4), and calcitonin. T3 and T4 are iodine-rich molecules that fuel metabolism. The thyroid hormones play several important roles in growth, metabolism, and development. The thyroid of pregnant women often become enlarged in late pregnancy to accommodate metabolic requirements of both the woman and the fetus.

Thyroid hormones accelerate metabolism in several ways. They promote normal growth of bones and increase growth hormone output. They increase the rate of lipid synthesis and mobilization. They increase cardiac output by increasing rate and strength of heart contractions. They can increase respiration, the number of red blood cells in the circulation, and the amount of oxygen carried in the blood. In addition, they promote normal nervous system development including nerve branching.

The parathyroids

While most people have four small parathyroid glands poised around the thyroid gland, about 14% of the population have one or two additional parathyroid glands. Because these oval glands are so small, the extra space occupied by extra glands does not seem to be a problem. The sole function of these glands is to regulate calcium levels in the body. Although this may seem like a simple task, the maintenance of specific calcium levels is critical. Calcium has numerous important bodily functions. Calcium makes up 2 to 3% of adult weight with roughly 99% of the calcium in bones. Calcium also plays a pivotal role in muscle contraction and neurotransmitter secretion.

The thymus

In young children, the thymus extends into the neck and the chest, but after puberty, it begins to shrink. The size of the thymus in most adults is very small. Like some other endocrine glands, the thymus has two lobes connected by a stalk. The thymus secretes several hormones that promote the maturation of different cells of the immune system in young children. In addition, the thymus oversees the development and learning of a particular type of immune system cell called a T lymphocyte, or T cell.

Although many details of thymal hormonal activity are not clear, at least four thymal products have been identified that control T cell and B cell (antibody-producing immune cells) maturation. The four products are: thymosin, thymic humoral factor (THF), thymic factor (TF), and thymopoietin. Because the viral disease, AIDS (acquired immune deficiency syndrome), is characterized by T cell depletion, some AIDS treatment approaches have tried administering tymosin to boost T cell production.

The pancreas

The pancreas is a large endocrine and exocrine gland situated below and behind the stomach in the lower abdomen. The pancreas is horizontally placed such that its larger end falls to the right and its narrower end to the left. Clusters of exocrine pancreatic cells called acini secrete digestive enzymes into the stomach; while endocrine cells secrete hormones responsible for maintaining blood glucose levels.

The endocrine cells of the pancreas are contained in the islets of Langerhans which are themselves embedded in a rich network of blood and lymph vessels. About one million islet cells make up about 2% of the total pancreas: the islet cells are quite small. The three major types of endocrine cells within the islets are alpha cells, beta cells, and delta cells. Beta cells make up about 70% of islet cells and secrete insulin.

Alpha cells, which secrete glucagon, comprise roughly 20% of islet cells. Delta cells, which comprise up to 8% of islet cells, secrete somatostatin. Another pancreatic hormone, called pancreatic polypeptide, is secreted by F cells in the islets and has just recently been characterized.

Insulin is secreted in response to high plasma glucose levels. Insulin facilitates glucose uptake into blood cells; thus, reducing plasma glucose levels. Glucagon has the opposite effect; low plasma glucose triggers the breakdown of stored glucogen in the liver and glucose release into the blood. By balancing these two hormones, the islets continually regulate circulating glucose levels. Both hormones are contained within secretory vesicles in the cells that release them. In addition, the monitoring of blood glucose concentrations are evaluated directly at the pancreas, as opposed to being mediated by another gland such as the pituitary. Moreover, nerve endings at the islets contribute in regulating insulin and glucagon secretion. The hormone somatotostatin is also released under conditions of increased blood glucose, glucagon, and amino acids. Somatostatin inhibits additional insulin release.

The overall effect of insulin is to store fuel in muscle and adipose tissue. It also promotes protein synthesis. Hence, insulin is said to be anabolic, which means that it works to build up instead of break down energy-storing molecules. Glucagon, however, is metabolic, since it promotes glycogen breakdown. However, each of the pancreatic hormones is also considered to be paracrine, since they also modulate other pancreatic cells.

Diabetes mellitus (DM) is a very serious endocrine disorder caused by insulin dysfunctions. In type I DM, the beta cells are defective and cannot produce enough insulin. Type II DM is caused by a lack of target cell-receptor responsiveness to available insulin. While type I requires regular insulin injections, type II can be controlled with diet.

The adrenals

One of the two adrenals sit atop each kidney and are divided into two distinct regions, the cortex and the medulla. The outer area makes up about 80% of each adrenal and is called the cortex. In addition, the inner portion is called the medulla. The adrenals provide the body with important buffers against stress while helping it adapt to stressful situations.

The cells of the cortex form three distinct layers, the zona glomerulosa (ZG), the zona fasciculata (ZF), and the zona reticularis (ZR). All three layers secrete steroid hormones. The ZG secretes mineralocorticoids; the ZF secretes glucocorticoids; and the ZR secretes primary androgens. Cholesterol droplets are interspersed throughout the cortex for synthesis of cortical steroids. ACTH released from the anterior pituitary triggers glucocorticoids release from the ZF. The major glucocorticoid in humans is cortisol, which fluctuates in concentration throughout the day: the highest levels exist in the morning around 8 A.M. with the lowest levels around midnight. Both physical and emotional stress can affect cortisol secretion. The major human mileralocorticoid is aldosterone. Aldosterone acts on the kidneys and is important in regulating fluid balance. It triggers increased extracellular fluid that leads to increased blood pressure.

Cells of the adrenal medulla, called chromaffin cells, secrete the hormones epinephrine (adrenaline) and non-epinephrine (nor-adrenaline). Chromaffin cells are neuroendocrine cells that function like some nerve fibers of the sympathetic nervous system. However, these cells are endocrine because the neuro-hormones that they release target distant organs. Although the effects of these two medullary hormones are the same whether they originate in the endocrine or the nervous system, endocrine hormonal effects are prolonged because they are removed more slowly from blood than from a nerve terminal. Both cortical and medullary hormones work together in emergencies, or stressful situations, to meet the physical demands of the moment.

The ovaries

The ovaries are located at the end of each fallopian tube in the female reproductive tract, and they produce the female reproductive hormones: estrogen, progesterone, and relaxin. Although the fluctuation of these hormones is critical to the female menstrual cycle, a hormone from the hypothalamus, called a releasing factor, initially triggers them. They enable gonadotrophs in the pituitary to release LH and FSH that, in turn, regulate part of the menstrual cycle. All of these hormones work together as part of the endocrine system to ensure fertility. They are also important for the development of sexual characteristics during puberty.

Each month after puberty, females release a single egg (ovulation) when the pituitary releases LH. Prior to ovulation, the maturing egg releases increasing levels of estrogen that inform the pituitary to secrete LH. While an egg travels down the fallopian tube, progesterone is released that prevents another egg from beginning to mature. Once an egg is shed in the uterine lining (in menstruation) the cycle can begin again. During pregnancy, high levels of circulating estrogen and progesterone prevent another egg from maturing. Estrogen levels fall dramatically at menopause, signifying the end of menstrual cycling and fertility. Menopause usually occurs between the ages of 40 and 50 years.

Endocrine regulation of the female reproductive tract does not stop during pregnancy. In fact, more sex hormones are released during pregnancy than during any other phase of female life. At this time, a new set of conditions support and protect the developing baby. Even cells of the developing embryo begin to release some hormones that keep the uterine lining intact for the first couple of months of pregnancy. High progesterone levels prevent the uterus from contracting so that the embryo is not disturbed. Progesterone also helps to prepare breasts for lactation. Towards the end of pregnancy, high estrogen levels stimulate the pituitary to release the hormone, oxytocin, which triggers uterine contractions. Prior to delivery, the ovaries release the hormone, relaxin, a protein which causes the pelvic ligaments to become loose for labor.

The testes

The two testes are located in the scrotum, which hangs between the legs behind the penis. The testes is devoted primarily to sperm production, but the remaining cells, called Leydig cells, produce testosterone. Testosterone caries out two important endocrine tasks in males: it facilitates sexual maturation, and it enables sperm to mature to a reproductively competent form. Healthy men remain capable of fertilizing an egg throughout their post-pubertal life. However, testosterone levels do show a gradual decline after about the age of 40 years with a total drop of around 20% by age 80 years.

Testosterone also has the important endocrine function of providing sexual desire in both men and women. Although reproduction can occur without maximal desire, this added incentive increases the likelihood of reproduction. Human sexual behavior is also influenced by several other factors including thoughts and beliefs.

Endocrine disorders

As much as 10% of the population will experience some endocrine disorder in their lifetime. Most endocrine disorders are caused by a heightened or diminished level of particular hormones. For example, excess growth hormone can cause giantism (unusually large stature). Tumors in endocrine glands are one of the major causes of hormone overproduction.

KEY TERMS

Exocrine— Glands with ducts that direct hormones to a specific target.

Hormone underproduction is often due to a mutation in the gene that codes for a particular hormone or the hormone’s receptor; even if the hormone is normal, a defective receptor can render the hormone ineffective in eliciting a response. The distinction between the pancreatic endocrine disorders, diabetes mellitus types I and II, make this point very clearly. In addition, underproduction of growth hormones can lead to dwarfism. Insufficient calcitonin from the thyroid can also lead to cretinism that is also characterized by diminished stature due to low calcium availability for bone growth.

The importance of diet can not be overlooked in some endocrine disorders. For example, insufficient dietary iodine (required for T3 and T4 synthesis) can cause goiters. Goiters are enlarged thyroid glands caused by the thyroid’s attempt to compensate for low iodine with increased size. Certain endocrine imbalances can also cause mental problems ranging from poor ability to concentrate to mental retardation (as in cretinism).

See also Chemoreception.

Resources

BOOKS

Germann, William J. Principles of Human Physiology. San Francisco, CA: Pearson Benjamin Cummings, 2005.

Greenstein, Ben. The Endocrine System at a Glance. Malden, MA: Blackwell Publishing, 2006.

Rushton, Lynette. The Endocrine System. Philadelphia, PA: Chelsea House Publishers, 2004.

Van De Graaff, Kent M., and R. Ward Rhees, eds. Human Anatomy and Physiology: Based on Schaum’s Outline of Theory and Problems of Human Anatomy and Physiology. New York: McGraw-Hill, 2001.

Louise Dickerson

Endocrine system

The endocrine system is the body's network of nine glands and over 100 hormones which maintain and regulate numerous events throughout the body. The glands of the endocrine system include the pituitary, thyroid, parathyroids, thymus, pancreas, pineal, adrenals , and ovaries or testes: in addition, the hypothalamus, in the brain , regulates the release of pituitary hormones. Each of these glands secrete hormones (chemical messengers) into the blood stream. Once hormones enter the blood, they travel throughout the body and are detected by receptors that recognize specific hormones. These receptors exist on target cells and organs. Once a target site is bound by a particular hormone, a cascade of cellular events follows that culminates in the physiological response to a particular hormone.

The endocrine system differs from the exocrine system in that exocrine glands contain ducts which direct their hormones to specific sites; whereas endocrine hormones travel through blood until they reach their destination. The endocrine is also similar to the nervous system , because both systems regulate body events and communicate through chemical messengers with target cells. However, the nervous system transmits neurotransmitters (also chemical messengers) between neighboring neurons via nerve extension, and neurotransmitters do not generally enter the circulation. Yet, some overlap between hormones and neurotransmitters exists which gives rise to chemical signals called neurohormones which function as part of the neuroendocrine system. The endocrine system oversees many critical life processes involving metabolism , growth, reproduction, immunity, and homeostasis . The branch of medicine that studies endocrine glands and the hormones which they secrete is called endocrinology.

History of endocrinology

Although some ancient cultures noted biological observations grounded in endocrine function, modern understanding of endocrine glands and how they secrete hormones has evolved only in the last 300 years. Ancient Egyptian and Chinese civilizations castrated (removed the testicles of) a servile class of men called eunuchs. It was noted that eunuchs were less aggressive than other men, but the link of this behavior to testosterone was not made until recently.

Light was shed on endocrine function during the seventeenth and eighteenth centuries by a few significant advances. A seventeenth century English scientist, Thomas Wharton (1614-1673), noted the distinction between ductile and ductless glands. In the 1690s, a Dutch scientist named Fredrik Ruysch (1638-1731) first stated that the thyroid secreted important substances into the blood stream. A few decades later, Theophile Bordeu (1722-1776) claimed that "emanations" were given off by some body parts that influenced functions of other body parts.

One of the greatest early experiments performed in endocrinology was published by A. A. Berthold (1803-1861) in 1849. Berthold took six young male chickens, and castrated four of them. The other two were left to develop normally and used comparatively as control samples. Two of the castrated chickens were left to become chicken eunuchs. But what Berthold did with the other two castrated chickens is what really changed endocrinology. He transplanted the testes back into these two chickens at a distant site from where they were originally. The two castrated chickens never matured into roosters with adult combs or feathers. But the chickens who received transplanted testes did mature into normal adult roosters. This experiment revealed that hormones that could access the blood stream from any site would function correctly in the body and that hormones did, in fact, travel freely in the circulation.

The same year Berthold published his findings, Thomas Addison (1793-1860), a British scientist reported one of the first well documented endocrine diseases which was later named Addison's disease (AD). AD patients all had a gray complexion with sickly skin; they also had weak hearts and insufficient blood levels of hemoglobin necessary for oxygen transport throughout the body. On autopsy, each of the patients Addison studied were found to have diseased adrenal glands. This disease can be controlled today if it is detected early. President John F. Kennedy suffered from AD.

Basic endocrine principles

Most endocrine hormones are maintained at specific concentrations in the plasma , the non-cellular, liquid portion of the blood. Receptors at set locations monitor plasma hormonal levels and inform the gland responsible for producing that hormone if levels are too high or too low for a particular time of day, month, or other life period. When excess hormone is present, a negative feedback loop is initiated such that further hormone production is inhibited. Most hormones have this type of regulatory control. However, a few hormones operate on a positive feedback cycle such that high levels of the particular hormone will activate release of another hormone. With this type of feedback loop, the end result is usually that the second hormone released will eventually decrease the initial hormone's secretion. An example of positive feedback regulation occurs in the female menstrual cycle , where high levels of estrogen stimulate release of the pituitary hormone, luteinizing hormone (LH).

All hormones are influenced by numerous factors. The hypothalamus can release inhibitory or stimulatory hormones the determine pituitary function. And every physiological component that enters the circulation can effect some endocrine function. Overall, this system uses multiple bits of chemical information to hormonally maintain a biochemically balanced organism .

Endocrine hormones do not fall into any one chemical class, but most are either a protein (polypeptides, peptides, and glycoproteins are also included in this category) or steroids. Protein hormones bind cell-surface receptors and activate intracellular events that carry out the hormone's response. Steroid hormones, on the other hand, usually travel directly into the cell and bind a receptor in the cell's cytoplasm or nucleus. From there, steroid hormones (bound to their receptors) interact directly with genes in the DNA to elicit a hormonal response.

The pituitary

The pituitary gland has long been called "the master gland," because it secretes multiple hormones which, in turn, trigger the release of other hormones from other endocrine sites. The pituitary is roughly situated behind the nose and is anatomically separated into two distinct lobes, the anterior pituitary (AP) and the posterior pituitary (PP). The entire pituitary hangs by a thin piece of tissue , called the pituitary stalk, beneath the hypothalamus in the brain. The AP and PP are sometimes called the adenohypophysis and neurohypophysis, respectively.

The PP secretes two hormones, oxytocin and antidiuretic hormone (ADH), under direction from the hypothalamus. Direct innervation of the PP occurs from regions of the hypothalamus called the supraoptic and paraventricular nuclei. Although the PP secretes its hormones into the bloodstream through blood vessels that supply it, it is regulated in a neuroendocrine fashion. The AP, on the other hand, receives hormonal signals from the blood supply within the pituitary stalk.

AP cells are categorized according to the hormones that they secrete. The hormone-producing cells of the AP include: somatotrophs, corticotrophs, thyrotrophs, lactotrophs, and gonadotrophs. Somatotrophs secrete growth hormone; corticotrophs secrete adrenocorticotropic hormone (ACTH); thyrotrophs secrete thyroid stimulating hormone (TSH); lactotrophs secrete prolactin; and gonadotrophs secrete LH and follicle stimulatory hormone (FSH). Each of these hormones sequentially signals a response at a target site. While ACTH, TSH, LH, and FSH primarily stimulate other major endocrine glands, growth hormone and prolactin primarily coordinate an endocrine response directly on bones and mammary tissue, respectively.

The pineal

The pineal gland is a small cone-shaped gland believed to function as a body clock. The pineal is located deep in the brain just below the rear-most portion of the corpus callosum (a thick stretch of nerves that connects the two sides of the brain). The pineal gland, also called the pineal body, has mystified scientists for centuries. The seventeenth century philosopher, Rene Descartes, speculated that the pineal was the seat of the soul. However, its real function is somewhat less grandiose than that.

The pineal secretes the hormone melatonin, which fluctuates on a daily basis with levels highest at night. Although its role is not well understood, some scientists believe that melatonin helps to regulate other diurnal events, because melatonin fluctuates in a 24-hour period. Exactly what controls melatonin levels is not well understood either; however, visual registration of light may regulate the cycle.

The thyroid

The thyroid is a butterfly-shaped gland that wraps around the back of the esophagus. The two lobes of the thyroid are connected by a band of tissue called the isthmus . An external covering of connective tissue separates each lobe into another 20-40 follicles. Between the follicles are numerous blood and lymph vessels in another connective tissue called stroma. The epithelial cells around the edge of the follicles produce the major thyroid hormones.

The major hormones produced by the thyroid are triiodothyronine (T3), thyroxine (T4), and calcitonin. T3 and T4 are iodine-rich molecules that fuel metabolism. The thyroid hormones play several important roles in growth, metabolism, and development. The thyroid of pregnant women often become enlarged in late pregnancy to accommodate metabolic requirements of both the woman and the fetus.

Thyroid hormones accelerate metabolism in several ways. They promote normal growth of bones and increase growth hormone output. They increase the rate of lipid synthesis and mobilization. They increase cardiac output by increasing rate and strength of heart contractions. They can increase respiration , the number of red blood cells in the circulation, and the amount of oxygen carried in the blood. In addition, they promote normal nervous system development including nerve branching.

The parathyroids

While most people have four small parathyroid glands poised around the thyroid gland, about 14% of the population have one or two additional parathyroid glands. Because these oval glands are so small, the extra space occupied by extra glands does not seem to be a problem. The sole function of these glands is to regulate calcium levels in the body. Although this may seem like a simple task, the maintenance of specific calcium levels is critical. Calcium has numerous important bodily functions. Calcium makes up 2-3% of adult weight with roughly 99% of the calcium in bones. Calcium also plays a pivotal role in muscle contraction and neurotransmitter secretion.

The thymus

In young children, the thymus extends into the neck and the chest, but after puberty , it begins to shrink. The size of the thymus in most adults is very small. Like some other endocrine glands, the thymus has two lobes connected by a stalk. The thymus secretes several hormones that promote the maturation of different cells of the immune system in young children. In addition, the thymus oversees the development and "education" of a particular type of immune system cell called a T lymphocyte, or T cell.

Although many details of thymal hormonal activity are not clear, at least four thymal products have been identified which control T cell and B cell (antibody-producing immune cells) maturation. The four products are: thymosin, thymic humoral factor (THF), thymic factor (TF), and thymopoietin. Because the viral disease, AIDS , is characterized by T cell depletion, some AIDS treatment approaches have tried administering tymosin to boost T cell production.

The pancreas

The pancreas is a large endocrine and exocrine gland situated below and behind the stomach in the lower abdomen. The pancreas is horizontally placed such that its larger end falls to the right and its narrower end to the left. Clusters of exocrine pancreatic cells called acini secrete digestive enzymes into the stomach; while endocrine cells secrete hormones responsible for maintaining blood glucose levels.

The endocrine cells of the pancreas are contained in the islets of Langerhans which are themselves embedded in a rich network of blood and lymph vessels. About one million islet cells make up about 2% of the total pancreas: the islet cells are quite small. The three major types of endocrine cells within the islets are alpha cells, beta cells, and delta cells. Beta cells make up about 70% of islet cells and secrete insulin . Alpha cells which secrete glucagon comprise roughly 20% of islet cells. Delta cells, which comprise up to 8% of islet cells, secrete somatostatin. Another pancreatic hormone, called pancreatic polypeptide, is secreted by F cells in the islets and has just recently been characterized.

Insulin is secreted in response to high plasma glucose levels. Insulin facilitates glucose uptake into blood cells thus reducing plasma glucose levels. Glucagon has the opposite effect; low plasma glucose triggers the breakdown of stored glucogen in the liver and glucose release into the blood. By balancing these two hormones, the islets continually regulate circulating glucose levels. Both hormones are contained within secretory vesicles in the cells which release them. And monitoring of blood glucose concentrations are evaluated directly at the pancreas, as opposed to being mediated by another gland such as the pituitary. In addition, nerve endings at the islets contribute in regulating insulin and glucagon secretion. The hormone somatotostatin is also released under conditions of increased blood glucose, glucagon, and amino acids. Somatostatin inhibits additional insulin release.

The overall effect of insulin is to store fuel in muscle and adipose tissue. It also promotes protein synthesis. Hence, insulin is said to be anabolic which means that it works to build up instead of break down energy-storing molecules. Glucagon, however, is metabolic, since it promotes glycogen breakdown. However, each of the pancreatic hormones is also considered to be paracrine, since they also modulate other pancreatic cells.

Diabetes mellitus (DM) is a very serious endocrine disorder caused by insulin dysfunctions. In type I DM, the beta cells are defective and can not produce enough insulin. Type II DM is caused by a lack of target cell-receptor responsiveness to available insulin. While type I requires regular insulin injections, type II can be controlled with diet.

The adrenals

One of the two adrenals sit atop each kidney and are divided into two distinct regions, the cortex and the medulla. The outer area makes up about 80% of each adrenal and is called the cortex. And the inner portion is called the medulla. The adrenals provide the body with important buffers against stress while helping it adapt to stressful situations.

The cells of the cortex form three distinct layers, the zona glomerulosa (ZG), the zona fasciculata (ZF), and the zona reticularis (ZR). All three layers secrete steroid hormones. The ZG secretes mineralocorticoids; the ZF secretes glucocorticoids; and the ZR secretes primary androgens. Cholesterol droplets are interspersed throughout the cortex for synthesis of cortical steroids. ACTH released from the anterior pituitary triggers glucocorticoids release from the ZF. The major glucocorticoid in humans is cortisol, which fluctuates in concentration throughout the day: the highest levels exist in the morning around 8 a.m. with the lowest levels around midnight. Both physical and emotional stress can affect cortisol secretion. The major human mileralocorticoid is aldosterone. Aldosterone acts on the kidneys and is important in regulating fluid balance. It triggers increased extracellular fluid that leads to increased blood pressure .

Cells of the adrenal medulla, called chromaffin cells, secrete the hormones epinephrine (adrenaline) and non-epinephrine (nor-adrenaline). Chromaffin cells are neuroendocrine cells which function like some nerve fibers of the sympathetic nervous system. However, these cells are endocrine, because the neurohormones that they release target distant organs. Although the effects of these two medullary hormones are the same whether they originate in the endocrine or the nervous system, endocrine hormonal effects are prolonged, because they are removed more slowly from blood than from a nerve terminal. Both cortical and medullary hormones work together in emergencies, or stressful situations, to meet the physical demands of the moment.

The ovaries

The ovaries are located at the end of each fallopian tube in the female reproductive tract, and they produce the female reproductive hormones: estrogen, progesterone, and relaxin. Although the fluctuation of these hormones is critical to the female menstrual cycle, they are initially triggered by a hormone from the hypothalamus, called a releasing factor, that enables gonadotrophs in the pituitary to release LH and FSH that, in turn, regulate part of the menstrual cycle. All of these hormones work together as part of the endocrine system to ensure fertility. They are also important for the development of sexual characteristics during puberty.

Each month after puberty, females release a single egg (ovulation) when the pituitary releases LH. Prior to ovulation, the maturing egg releases increasing levels of estrogen that inform the pituitary to secrete LH. While an egg travels down the fallopian tube, progesterone is released which prevents another egg from beginning to mature. Once an egg is shed in the uterine lining (in menstruation), the cycle can begin again. During pregnancy, high levels of circulating estrogen and progesterone prevent another egg from maturing. Estrogen levels fall dramatically at menopause , signifying the end of menstrual cycling and fertility. Menopause usually occurs between the ages of 40 and 50.

Endocrine regulation of the female reproductive tract does not stop during pregnancy. In fact, more sex hormones are released during pregnancy than during any other phase of female life. At this time, a new set of conditions support and protect the developing baby. Even cells of the developing embryo begin to release some hormones that keep the uterine lining intact for the first couple of months of pregnancy. High progesterone levels prevent the uterus from contracting so that the embryo is not disturbed. Progesterone also helps to prepare breasts for lactation. Towards the end of pregnancy, high estrogen levels stimulate the pituitary to release the hormone, oxytocin, which triggers uterine contractions. Prior to delivery, the ovaries release the hormone, relaxin, a protein which causes the pelvic ligaments to become loose for labor.

The testes

The two testes are located in the scrotum, which hangs between the legs behind the penis. Most of the testes is devoted to sperm production, but the remaining cells, called Leydig cells, produce testosterone. Testosterone caries out two very important endocrine tasks in males: it facilitates sexual maturation, and it enables sperm to mature to a reproductively-competent form. Healthy men remain capable of fertilizing an egg throughout their post-pubertal life. However, testosterone levels do show a gradual decline after about the age of 40 with a total drop of around 20% by age 80.

Testosterone also has the important endocrine function of providing sexual desire in both men and women. Although reproduction can occur without maximal desire, this added incentive increases the likelihood of reproduction. Human sexual behavior is also influenced by several other factors including thoughts and beliefs.

Endocrine disorders

As much as 10% of the population will experience some endocrine disorder in their lifetime. Most endocrine disorders are caused by a heightened or diminished level of particular hormones. For example, excess growth hormone can cause giantism (unusually large stature). Tumors in endocrine glands are one of the major causes of hormone overproduction.

Hormone underproduction is often due to a mutation in the gene that codes for a particular hormone or the hormone's receptor; even if the hormone is normal, a defective receptor can render the hormone ineffective in eliciting a response. The distinction between the pancreatic endocrine disorders, diabetes mellitus types I and II, make this point very clearly. In addition, underproduction of growth hormones can lead to dwarfism. Insufficient calcitonin from the thyroid can also lead to cretinism which is also characterized by diminished stature due to low calcium availability for bone growth.

The importance of diet can not be overlooked in some endocrine disorders. For example, insufficient dietary iodine (required for T3 and T4 synthesis) can cause goiters. Goiters are enlarged thyroid glands caused by the thyroid's attempt to compensate for low iodine with increased size. Certain endocrine imbalances can also cause mental problems ranging from poor ability to concentrate to mental retardation (as in cretinism).

See also Chemoreception.

Resources

books

Little, M. The Endocrine System. New York: Chelsea House Publishers, 1990.

Marieb, Elaine Nicpon. Human Anatomy & Physiology. 5th Edition. San Francisco: Benjamin/Cummings, 2000.

Louise Dickerson

KEY TERMS

Exocrine

—Glands with ducts that direct hormones to a specific target.

Endocrine system

Definition

The endocrine system is a widespread group of glands and organs that acts as the body's control system for producing, storing, and secreting chemical substances called hormones.

Description

The primary glands that compose the endocrine system are the hypothalamus, pituitary, thyroid, parathyroid, adrenal, pineal, ovary, and testes. The pancreas , considered both an organ and a gland, is also part of the system. The thymus is sometimes considered an endocrine-system organ. Although not part of the endocrine system, other organs that secrete hormones are the heart , brain , lungs , kidneys , liver , skin, and placenta. The word "endocrine" means that in response to specific stimuli, the hormones produced by the glands are released into the bloodstream.

Function

Hormones are compounds produced by the endocrine glands. They generally control the growth, development, and metabolism of the body; the electrolyte composition of body fluids; and reproduction. The specific functions of the endocrine glands and pancreas are unique.

Pituitary gland

The pituitary is the master gland of the endocrine system. Located at the base of the brain, the gland, which is about the size of a marble, consists of two parts: anterior and posterior. The anterior pituitary produces hormones that either stimulate other glands (such as adrenal, testis, ovary, and thyroid) to produce target-gland hormones, or directly affect the target organs.

Three of these hormones—adrenocorticotropic hormone (ACTH), gonadotropins, and thyroid-stimulating hormone (TSH)—act on other glands. ACTH stimulates the adrenal cortex to produce corticosteroid hormones and small amounts of male and female sex hormones. Gonadotropins are two hormones that regulate the production of male and female sex hormones and the egg (ova) and sperm (spermatozoa) cells. TSH stimulates the thyroid gland to produce and release thyroid hormone.

Another pituitary hormone, growth hormone (GH), has a central role in controlling the growth and development of the body and its components, including organs, tissue, and muscle. It also affects the metabolism of carbohydrates ,

protein, and fat. For example, GH increases glucose levels in the blood by reducing the amount of glucose used by muscle cells and adipose tissue and by promoting glucose production from certain liver molecules. Other functions of GH include increasing the amount of amino acids that cells take from the blood and stimulating the breakdown of lipids (fats ) in adipose tissue. The pituitary hormone prolactin acts with other hormones in female breast development and helps regulate breast-milk production (lactation ).

Two hormones, vasopressin and oxytocin, are stored but not produced in the posterior pituitary. Vasopressin, also called arginine vasopressin (AVP), helps the body to conserve water by increasing reabsorption of water from the kidneys. Oxytocin stimulates contractions in the uterus during childbirth and activates milk injection caused by an infant sucking on the breast.

Adrenal glands

The adrenals are small glands on top of the kidneys. The adrenals have two parts: an outer layer called the cortex, and an inner layer called the medulla. The adrenal cortex produces a variety of hormones called corticosteroids , including hydrocortisone (cortisol), which helps increase blood glucose levels. It also reduces the amount of glucose absorbed by muscles and adipose tissue. Another function of cortisol is to protect the body from the adverse affects of stress , including emotional and physical trauma.

The adrenal medulla produces adrenaline and noradrenaline, substances that increase the heart rate and blood pressure during times of stress. Their action is referred to as the "fight-or-flight" response.

Thyroid gland

The thyroid gland is composed of two sections in front of the windpipe and below the voice box. It produces two hormones, thyroxine (T4) and tri-iodothyronine (T3), which together are called the thyroid hormones. They help regulate growth and development and help in childhood brain development. The thyroid also contains cells that produce the hormone calcitonin, which helps to maintain normal calcium levels in the blood.

Parathyroid glands

The parathyroid complex is composed of four small glands, each the size of a pea, and each located on the four corners of the thyroid gland. They secrete parathyroid hormone, which regulates calcium levels in the blood.

Pancreas

The pancreas is located in the upper abdomen, just behind and below the stomach . It has two functions: to produce various enzymes that aid in digestion; and to produce insulin and glucagon, hormones that are key to the body's management of glucose (sugar) in the blood.

The primary purpose of insulin is to lower blood-glucose levels in the body. It helps form glycogen, proteins , and lipids, which are stored in the body (usually in the liver, muscles, and adipose tissue) to be used for energy. Glucagon increases blood-glucose levels, an action opposite to that of insulin. A strict balance between the glucagon and insulin is required to maintain proper blood-sugar levels.

Hypothalamus

Located deep inside the brain, the hypothalamus maintains direct control of the pituitary gland . It acts as the central "control room" of the endocrine system, directing the activities of the other parts of the system. These activities include regulating eating and drinking, sexual behavior, blood pressure, heart rate, body temperature, emotions, and the sleeping/waking cycle. When the brain receives information indicating that hormonal changes are needed somewhere in the body, the hypothalamus secretes chemicals that stimulate or suppress hormone production in the pituitary gland.

Pineal and thymus

The pineal is located in the center of the brain. This gland secretes melatonin, a hormone that helps regulate the sleeping/waking cycle. Disturbances in the production of melatonin causes jet lag, experienced by many long-distance travelers. Melatonin also influences development of the male and female sex glands. The thymus processes lymphocytes in infants and is partly responsible for immune-system development.

Ovaries and testes

The ovaries and testes, also called the sex glands, produce cells and hormones essential to reproduction and development of the body, including male and female sex characteristics. The three types of sex hormones are estrogens, progestogens, and androgens (including testosterone).

The main role of estrogens is to coordinate development and function of the female genitalia and breasts. Estrogens are also associated with the start of the menstrual bleeding cycle. Estrogen production in the ovary ceases during menopause . Estrogen is also produced in men (by the testes), though at lower levels than occur in women.

Progestogens are produced in the ovaries during part of the menstrual cycle, and in the placenta during pregnancy . They cause changes in the lining of the uterus to prepare it for pregnancy, and they act with estrogens to stimulate mammary-gland development in the breasts to prepare for lactation. Progesterone is the main progestogen hormone.

The primary androgen produced in the testes is the steroid testosterone. While mainly associated with male development, testosterone is produced in small amounts in women by the ovaries. During pregnancy, testosterone helps to develop the internal and external male sex organs. In males, testosterone promotes the growth of the sex organs and develops or stimulates male characteristics, such as deepening voice; growth of facial, pubic, and other body hair; and muscle growth and strength. In adult males, testosterone maintains the masculine characteristics and sexual potency and regulates sperm production.

Role in human health

A wide variety and dozens of symptoms can indicate a hormonal imbalance in the body. However, a specific group of symptoms give an initial indication of a problem in the endocrine system. For example, excessive thirst, frequent urination, and unexplained weight loss are classic signs of diabetes mellitus , the most common endocrine disorder. Many primary-care physicians still treat endocrine problems, especially diabetes, themselves. However, the primary care doctor often makes a preliminary diagnosis and then refers the patient to an endocrine-system specialist, called an endocrinologist.

Disorders of the endocrine system often, but not always, result from an over-or underproduction of a particular hormone. Too much or too little of a hormone can be harmful. The endocrine organs use a feedback mechanism to regulate hormone levels. It acts much like a household thermostat, increasing production of a specific hormone when it detects too little in the blood, or decreasing production when it detects too much or the right amount. Tight control of hormone levels is needed for the body to function properly. The endocrine organs secrete hormones directly into the bloodstream, where special proteins usually bind to them, helping to maintain them as they travel through the body.

Common diseases and disorders

There are two basic classes of endocrine disorders: problems associated with hormone-production levels, and problems caused by tissues that are unable to respond to hormones. Hormone-production disorders are broken into two groups: insufficient hormone production, called hypofunction; and too much hormone production, called hyperproduction. Endocrine-system disorders include the following:

• Diabetes mellitus is a disease that includes type 1 and type 2 diabetes. Type 1 is an autoimmune disease caused when the immune system destroys certain insulin-producing cells in the pancreas. This causes the pancreas to produce little or no insulin. Type 1 diabetes usually develops in children and young adults, but it can appear at any age. Symptoms include increased thirst and urination, unexplained weight loss, blurred vision , and extreme fatigue. There is no cure; insulin, first used in 1921, remains the only treatment. Type 2 diabetes accounts for 90% to 95% of diabetes cases. It usually develops in adults over age 40 and is usually associated with obesity . In type 2, the pancreas produces insulin, but the hormone is not used effectively by the body, a condition called insulin resistance. Several years after onset, insulin production decreases below the level needed to maintain glucose homeostasis. The result is the same as for type 1 diabetes: glucose builds up in the blood because the body cannot use it efficiently. Symptoms develop gradually and include increased thirst and urination, weight loss, fatigue, nausea, blurred vision, frequent infections, and wounds or sores that heal slowly. Insulin resistance is treated with drugs such as thiazolidinedions (rosiglitazone and pioglitazone) and biguanides (metformen). When insufficient insulin is produced, type 2 diabetes appears. However, research indicates progression of insulin resistance to type 2 diabetes can usually be halted or slowed with the insulin-resistance medications, or by lifestyle changes that result in weight loss.
• Hypothyroidism is caused by the thyroid gland producing too little thyroid hormone. It can lead to severe hypothyroidism, a disorder that usually develops after age 40. Symptoms include intolerance to cold, lethargy, fatigue, weight gain, and mental sluggishness. Congenital hypothyroidism is present at birth and has the same symptoms. If left untreated, it can lead to mental retardation. The standard treatment for both hypothyroid disorders is thyroid hormone-replacement medications such as levothyroxine (Synthroid, Unithroid, Levoxyl, and Levothroid) and triiodothyrine.
• Hyperthyroidism is due to an excess of thyroid hormones and affects women more frequently than men. Symptoms include nervousness, weight loss, intolerance to heat, diarrhea , heart palpitations, and insomnia. Some patients experience protruding eyes and trembling. Treatments include medications to inhibit thyroid-hormone production, and removal or destruction of the thyroid gland with radioactive iodine. The most common cause of the excessive thyroid production is Graves' disease, an autoimmune disorder of the thyroid gland.
• Addison's disease is caused by underactivity or immune-system destruction of the adrenal gland. It can be life-threatening if left untreated. Symptoms include weakness, fatigue, nausea, dehydration , fever , and hyperpigmentation (darkening of the skin without sun exposure.) The standard treatment is with corticosteroid hormones and adequate dietary salt.
• Cushing's syndrome and Cushing's disease are different disorders with similar symptoms: obesity, weakness, easily bruised skin, acne, and hypertension (high blood pressure.) Cushing's syndrome is usually caused by excessive production of glucocorticoid hormones in the adrenal gland. However, it can sometimes be caused by benign or cancerous tumors of the adrenal gland. Cushing's disease usually results from the overproduction of the adrenocoticotropic hormone in the pituitary gland, due to a benign tumor. Treatment for both disorders can include surgery, radiation therapy, chemotherapy , and blocking production of the glucorticoid hormones with drugs.
• Less common endocrine disorders include acromegaly, gigantism, and hypogonadism. Acromegaly occurs in adults and gigantism in children. Both are caused by a pituitary tumor that spurs overproduction of growth hormone. Hypogonadism causes delayed sexual maturity in children and infertility in adults. It is caused by underproduction of follicle-stimulating hormone (FSH) in the pituitary gland.

KEY TERMS

Adipose tissue —Connective tissue in which fat is stored and that has the cells distended by droplets of fat.

Autoimmune —A term that refers to a condition in which antibodies or T cells attack the molecules, cells, or tissue of the body organ or system producing them.

Electrolyte —A nonmetallic electric conductor in which current is carried by ion movement.

Lactation —The secretion of milk by the mammary gland in the breasts.

Lymphocytes —Weak cells produced in the lymphoid tissue.

Menopause —The period when natural menstruation stops, usually between ages of 45 and 50.

Menstruation —The discharge of blood from the uterus that occurs in approximately monthly intervals in females, starting at puberty.

Resources

BOOKS

Constanti, A., et al. Basic Endocrinology for Students of Pharmacy and Allied Health Sciences. Newark, NJ: Harwood Academic, 1998.

Hall, J. E., and L. Nieman, editors. Handbook of Diagnostic Endocrinology. Totowa, NJ: Humana Press, 2001.

Krentz, A. Churchill's Pocket Book of Diabetes. New York: Churchill Livingston, 2001.

Matthew, N. J. How the Endocrine System Works. Malden, MA: Blackwell Science, 2001.

Wilson, J. D., et al. Williams Textbook of Endocrinology. St. Louis, MO: W. B. Saunders, 1998.

PERIODICALS

American Diabetes Association. "Implications of the Diabetes Control and Complications Study." Diabetes Care (January 2001): 825.

Elliott, B. "Diagnosing and Treating Hypothyroidism." The Nurse Practitioner (March 2000): 92+.

Emanuele, N. and M. A. "The Endocrine System: Alcohol Alters Critical Hormonal Balance." Alcohol Health and Research World (Winter 1997): 53-64.

Hiller-Sturmhofel, S., and A. Bartke. "The Endocrine System: An Overview." Alcohol Health and Research World (Summer 1998): 153-154.

Lamberts, S. W. J., et al. "The Endocrinology of Aging." Science (October 17, 1997): 419-424.

Wilson, J. D. "Prospects for Research for Disorders of the Endocrine System." Journal of the American Medical Association (February 7, 2001): 624.

ORGANIZATIONS

American Association of Clinical Endocrinologists. 1000 Riverside Avenue, Suite 205, Jacksonville, FL 32204.(904) 353-7878. <http://www.aace.com>.

American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 342-2383. <http://www.diabetes.org>.

American Thyroid Association. Montefiore Medical Center, 111 East 210th Street, Room 311, Bronx, NY 10467.(718) 882-6085. <http://www.thyroid.org>.

Endocrine Society. 4350 East West Highway, Suite 500, Bethesda, MD 20814. (301) 941-0200. <http://www.endo-society.org>.

Ken R. Wells

Endocrine System

Definition

The endocrine system is a widespread group of glands and organs that acts as the body's control system for producing, storing, and secreting chemical substances called hormones.

Description

The primary glands that compose the endocrine system are the hypothalamus, pituitary, thyroid, parathyroid, adrenal, pineal, ovary, and testes. The pancreas, considered both an organ and a gland, is also part of the system. The thymus is sometimes considered an endocrine-system organ. Although not part of the endocrine system, other organs that secrete hormones are the heart, brain, lungs, kidneys, liver, skin, and placenta. The word "endocrine" means that in response to specific stimuli, the hormones produced by the glands are released into the bloodstream.

Function

Hormones are compounds produced by the endocrine glands. They generally control the growth, development, and metabolism of the body; the electrolyte composition of body fluids; and reproduction. The specific functions of the endocrine glands and pancreas are unique.

Pituitary gland

The pituitary is the master gland of the endocrine system. Located at the base of the brain, the gland, which is about the size of a marble, consists of two parts: anterior and posterior. The anterior pituitary produces hormones that either stimulate other glands (such as adrenal, testis, ovary, and thyroid) to produce target-gland hormones, or directly affect the target organs.

Three of these hormones—adrenocorticotropic hormone (ACTH), gonadotropins, and thyroid-stimulating hormone (TSH)—act on other glands. ACTH stimulates the adrenal cortex to produce corticosteroid hormones and small amounts of male and female sex hormones. Gonadotropins are two hormones that regulate the production of male and female sex hormones and the egg (ova) and sperm (spermatozoa) cells. TSH stimulates the thyroid gland to produce and release thyroid hormone.

Another pituitary hormone, growth hormone (GH), has a central role in controlling the growth and development of the body and its components, including organs, tissue, and muscle. It also affects the metabolism of carbohydrates, protein, and fat. For example, GH increases glucose levels in the blood by reducing the amount of glucose used by muscle cells and adipose tissue and by promoting glucose production from certain liver molecules. Other functions of GH include increasing the amount of amino acids that cells take from the blood and stimulating the breakdown of lipids (fats) in adipose tissue. The pituitary hormone prolactin acts with other hormones in female breast development and helps regulate breast-milk production (lactation ).

Two hormones, vasopressin and oxytocin, are stored but not produced in the posterior pituitary. Vasopressin, also called arginine vasopressin (AVP), helps the body to conserve water by increasing reabsorption of water from the kidneys. Oxytocin stimulates contractions in the uterus during childbirth and activates milk injection caused by an infant sucking on the breast.

Adrenal glands

The adrenals are small glands on top of the kidneys. The adrenals have two parts: an outer layer called the cortex, and an inner layer called the medulla. The adrenal cortex produces a variety of hormones called corticosteroids, including hydrocortisone (cortisol), which helps increase blood glucose levels. It also reduces the amount of glucose absorbed by muscles and adipose tissue. Another function of cortisol is to protect the body from the adverse affects of stress, including emotional and physical trauma.

The adrenal medulla produces adrenaline and noradrenaline, substances that increase the heart rate and blood pressure during times of stress. Their action is referred to as the "fight-or-flight" response.

Thyroid gland

The thyroid gland is composed of two sections in front of the windpipe and below the voice box. It produces two hormones, thyroxine (T4) and triiodothyronine (T3), which together are called the thyroid hormones. They help regulate growth and development and help in childhood brain development. The thyroid also contains cells that produce the hormone calcitonin, which helps to maintain normal calcium levels in the blood.

Parathyroid glands

The parathyroid complex is composed of four small glands, each the size of a pea, and each located on the four corners of the thyroid gland. They secrete parathyroid hormone, which regulates calcium levels in the blood.

Pancreas

The pancreas is located in the upper abdomen, just behind and below the stomach. It has two functions: to produce various enzymes that aid in digestion; and to produce insulin and glucagon, hormones that are key to the body's management of glucose (sugar) in the blood.

The primary purpose of insulin is to lower blood-glucose levels in the body. It helps form glycogen, proteins, and lipids, which are stored in the body (usually in the liver, muscles, and adipose tissue) to be used for energy. Glucagon increases blood-glucose levels, an action opposite to that of insulin. A strict balance between the glucagon and insulin is required to maintain proper blood-sugar levels.

Hypothalamus

Located deep inside the brain, the hypothalamus maintains direct control of the pituitary gland. It acts as the central "control room" of the endocrine system, directing the activities of the other parts of the system. These activities include regulating eating and drinking, sexual behavior, blood pressure, heart rate, body temperature, emotions, and the sleeping/waking cycle. When the brain receives information indicating that hormonal changes are needed somewhere in the body, the hypothalamus secretes chemicals that stimulate or suppress hormone production in the pituitary gland.

Pineal and thymus

The pineal is located in the center of the brain. This gland secretes melatonin, a hormone that helps regulate the sleeping/waking cycle. Disturbances in the production of melatonin causes jet lag, experienced by many long-distance travelers. Melatonin also influences development of the male and female sex glands. The thymus processes lymphocytes in infants and is partly responsible for immune-system development.

Ovaries and testes

The ovaries and testes, also called the sex glands, produce cells and hormones essential to reproduction and development of the body, including male and female sex characteristics. The three types of sex hormones are estrogens, progestogens, and androgens (including testosterone).

The main role of estrogens is to coordinate development and function of the female genitalia and breasts. Estrogens are also associated with the start of the menstrual bleeding cycle. Estrogen production in the ovaries ceases during menopause. Estrogen is also produced in men (by the testes), though at lower levels than occur in women.

Progestogens are produced in the ovaries during part of the menstrual cycle, and in the placenta during pregnancy. They cause changes in the lining of the uterus to prepare it for pregnancy, and they act with estrogens to stimulate mammary-gland development in the breasts to prepare for lactation. Progesterone is the main progestogen hormone.

The primary androgen produced in the testes is the steroid testosterone. While mainly associated with male development, testosterone is produced in small amounts in women by the ovaries. During pregnancy, testosterone helps to develop the internal and external male sex organs. In males, testosterone promotes the growth of the sex organs and develops or stimulates male characteristics, such as deepening voice; growth of facial, pubic, and other body hair; and muscle growth and strength. In adult males, testosterone maintains the masculine characteristics and sexual potency and regulates sperm production.

Role in human health

A wide variety and dozens of symptoms can indicate a hormonal imbalance in the body. However, a specific group of symptoms give an initial indication of a problem in the endocrine system. For example, excessive thirst, frequent urination, and unexplained weight loss are classic signs of diabetes mellitus, the most common endocrine disorder. Many primary care physicians still treat endocrine problems, especially diabetes, themselves. However, the primary care doctor often makes a preliminary diagnosis and then refers the patient to an endocrine-system specialist, called an endocrinologist.

Disorders of the endocrine system often, but not always, result from an over- or underproduction of a particular hormone. Too much or too little of a hormone can be harmful. The endocrine organs use a feedback mechanism to regulate hormone levels. It acts much like a household thermostat, increasing production of a specific hormone when it detects too little in the blood, or decreasing production when it detects too much or the right amount. Tight control of hormone levels is needed for the body to function properly. The endocrine organs secrete hormones directly into the bloodstream, where special proteins usually bind to them, helping to maintain them as they travel through the body.

KEY TERMS

Adipose tissue— Connective tissue in which fat is stored and that has the cells distended by droplets of fat.

Autoimmune— A term that refers to a condition in which antibodies or T cells attack the molecules, cells, or tissue of the body organ or system producing them.

Electrolyte— A nonmetallic electric conductor in which current is carried by ion movement.

Lactation— The secretion of milk by the mammary gland in the breasts.

Lymphocytes— Weak cells produced in the lymphoid tissue.

Menopause— The period when natural menstruation stops, usually between ages of 45 and 50.

Menstruation— The discharge of blood from the uterus that occurs in approximately monthly intervals in females, starting at puberty.

Common diseases and disorders

There are two basic classes of endocrine disorders: problems associated with hormone-production levels, and problems caused by tissues that are unable to respond to hormones. Hormone-production disorders are broken into two groups: insufficient hormone production, called hypofunction; and too much hormone production, called hyperproduction. Endocrine-system disorders include the following:

• Diabetes mellitus is a disease that includes type 1 and type 2 diabetes. Type 1 is an autoimmune disease caused when the immune system destroys certain insulin-producing cells in the pancreas. This causes the pancreas to produce little or no insulin. Type 1 diabetes usually develops in children and young adults, but it can appear at any age. Symptoms include increased thirst and urination, unexplained weight loss, blurred vision, and extreme fatigue. There is no cure; insulin, first used in 1921, remains the only treatment. Type 2 diabetes accounts for 90-95% of diabetes cases. It usually develops in adults over age 40 and is usually associated with obesity. In type 2, the pancreas produces insulin, but the hormone is not used effectively by the body, a condition called insulin resistance. Several years after onset, insulin production decreases below the level needed to maintain glucose homeostasis. The result is the same as for type 1 diabetes: glucose builds up in the blood because the body cannot use it efficiently. Symptoms develop gradually and include increased thirst and urination, weight loss, fatigue, nausea, blurred vision, frequent infections, and wounds or sores that heal slowly. Insulin resistance is treated with drugs such as thiazolidinedions (rosiglitazone and pioglitazone) and biguanides (metformen). When insufficient insulin is produced, type 2 diabetes appears. However, research indicates progression of insulin resistance to type 2 diabetes can usually be halted or slowed with the insulinresistance medications, or by lifestyle changes that result in weight loss.
• Hypothyroidism is caused by the thyroid gland producing too little thyroid hormone. It can lead to severe hypothyroidism, a disorder that usually develops after age 40. Symptoms include intolerance to cold, lethargy, fatigue, weight gain, and mental sluggishness. Congenital hypothyroidism is present at birth and has the same symptoms. If left untreated, it can lead to mental retardation. The standard treatment for both hypothyroid disorders is thyroid hormone-replacement medications such as levothyroxine (Synthroid, Unithroid, Levoxyl, and Levothroid) and tri-iodothyrine.
• Hyperthyroidism is due to an excess of thyroid hormones and affects women more frequently than men. Symptoms include nervousness, weight loss, intolerance to heat, diarrhea, heart palpitations, and insomnia. Some patients experience protruding eyes and trembling. Treatments include medications to inhibit thyroid-hormone production, and removal or destruction of the thyroid gland with radioactive iodine. The most common cause of the excessive thyroid production is Graves' disease, an autoimmune disorder of the thyroid gland.
• Addison's disease is caused by underactivity or immune-system destruction of the adrenal gland. It can be life-threatening if left untreated. Symptoms include weakness, fatigue, nausea, dehydration, fever, and hyperpigmentation (darkening of the skin without sun exposure.) The standard treatment is with corticosteroid hormones and adequate dietary salt.
• Cushing's syndrome and Cushing's disease are different disorders with similar symptoms: obesity, weakness, easily bruised skin, acne, and hypertension (high blood pressure.) Cushing's syndrome is usually caused by excessive production of glucocorticoid hormones in the adrenal gland. However, it can sometimes be caused by benign or cancerous tumors of the adrenal gland. Cushing's disease usually results from the overproduction of the adrenocoticotropic hormone in the pituitary gland, due to a benign tumor. Treatment for both disorders can include surgery, radiation therapy, chemotherapy, and blocking production of the glucorticoid hormones with drugs.
• Less common endocrine disorders include acromegaly, gigantism, and hypogonadism. Acromegaly occurs in adults and gigantism in children. Both are caused by a pituitary tumor that spurs overproduction of growth hormone. Hypogonadism causes delayed sexual maturity in children and infertility in adults. It is caused by underproduction of folliclestimulating hormone (FSH) in the pituitary gland.

Resources

BOOKS

Constanti, A., et al. Basic Endocrinology for Students of Pharmacy and Allied Health Sciences. Newark, NJ: Harwood Academic, 1998.

Hall, J. E., and L. Nieman, editors. Handbook of Diagnostic Endocrinology. Totowa, NJ: Humana Press, 2003.

Krentz, A. Churchill's Pocket Book of Diabetes. New York: Churchill Livingston, 2001.

Matthew, N. J. How the Endocrine System Works. Malden, MA: Blackwell Science, 2001.

Wilson, J. D., et al. Williams Textbook of Endocrinology. St. Louis, MO: W. B. Saunders, 2002.

PERIODICALS

American Diabetes Association. "Implications of the Diabetes Control and Complications Study." Diabetes Care (January 2001): 825.

Elliott, B. "Diagnosing and Treating Hypothyroidism." The Nurse Practitioner (March 2000): 92+.

Emanuele, N. and M. A. "The Endocrine System: Alcohol Alters Critical Hormonal Balance." Alcohol Health and Research World (Winter 1997): 53-64.

Hiller-Sturmhofel, S., and A. Bartke. "The Endocrine System: An Overview." Alcohol Health and Research World (Summer 1998): 153-154.

Lamberts, S. W. J., et al. "The Endocrinology of Aging." Science (October 17, 1997): 419-424.

Wilson, J. D. "Prospects for Research for Disorders of the Endocrine System." The Journal of the American Medical Association (February 7, 2001): 624.

ORGANIZATIONS

American Association of Clinical Endocrinologists. 1000 Riverside Avenue, Suite 205, Jacksonville, FL 32204. (904) 353-7878. 〈http://www.aace.com〉.

American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 342-2383. 〈http://www.diabetes.org〉.

American Thyroid Association. Montefiore Medical Center, 111 East 210th Street, Room 311, Bronx, NY 10467. (718) 882-6085. 〈http://www.thyroid.org〉.

Endocrine Society. 4350 East West Highway, Suite 500, Bethesda, MD 20814. (301) 941-0200. 〈http://www.endo-society.org〉.

ENDOCRINE SYSTEM

Among the most intellectually compelling theories of aging are those based on the notion that selection pressure favors those mechanisms which increase the probability of reproductive success (i.e., of producing a next generation of viable offspring). This relationship would be true even if, for example, the mechanisms utilized early in life to assure reproductive success ultimately contribute to senescence and reduce the longevity of postreproductive-age adults (Rose). The dual and apparently contradictory nature of this particular proposal is reflected in the term used to describe it, "antagonistic pleiotropy." Similar to antagonistic pleiotropy is another hypothesis called the "disposable soma." According to this view, the soma (body) is principally a vehicle for reproduction that becomes disposable once reproductive success has been achieved. In practice, this means that the resources of the body are targeted to assuring the perpetuation of the species instead of being distributed in a manner that may also help increase life span (Kirkwood).

Reproduction, including the antecedent development of reproductive organs and secondary sexual characteristics, is under strong hormonal control. If aging and life span are linked to the cessation of reproductive activity, as proposed above, then it follows that hormones likely play an important role in these events. In humans the most prominent sex hormones are the steroids estrogen (estradiol), progesterone, and testosterone. Of these, estrogen has probably received the greatest attention as a putative regulator of the aging process. Estrogen availability and levels determine the occurrence of two landmark events in the life cycle of women, menarche and menopause, and its virtual disappearance in postmenopausal women is associated with a variety of disorders and regressive tissue changes commonly associated with aging (Perry). These associations include the loss of bone (osteoporosis) and changes in skin texture, and the increased risk of cataracts, cardiovascular disease, and dementia. In addition, because of the reciprocal relationship between hormone levels and, for example, bone loss, estrogen has been used extensively in hormone replacement therapy (HRT), the goal being to counteract the negative effects of postmenopausal estrogen deficiency, that is, those changes commonly associated with aging (Palacios). Thus, by this criterion, estrogen is an antiaging hormone.

While estrogen is almost certainly the most widely recognized sex hormone that likely plays a role in aging, it is not the only sex hormone that has this distinction. There are two others that also have gained significant attention. One of these is testosterone, which was recognized many years ago, albeit indirectly, as an agent (factor) important in maintaining the vigor and general vitality of older males. This association had its origins in nineteenth-century research involving testicular transplants in animals (the goal being to restore the sexual activity of valuable old, stud animals), and progressed to the use of both transplants and testicular extracts in middle-aged to elderly human males (Gosden). This early work gave results that were at best equivocal, but it did establish the basis for research on hormone isolation and characterization, and the rationale for the use of testosterone in HRT. Testosterone levels in men do decline with age (the phenomenon is called andropause ), and low levels of the hormone have been equated with the loss of libido and cognitive skills, physical frailty, and bone loss. Testosterone HRT is an accepted form of therapy, particularly for men who are clearly hypogonadal (defined as bioavailable testosterone below the reference range for young men), but its widespread use remains controversial because of side effects (Bain).

The other sex steroid that has been widely implicated in the aging process is dehydroepiandrosterone (DHEA). DHEA is a weak androgen, produced by the adrenal gland, that can act directly on target tissues or indirectly as a precursor molecule for both estrogen and testosterone. DHEA, and its sulfated derivative DHEA-S, reach peak levels in young adults and decline steadily thereafter in most individuals. The blood levels at age eighty-five are, on average, about 10 percent of that in young adults. This diminution in DHEA/DHEA-S is called adrenopause. Lower levels of the hormone have been associated with age-related changes in body composition, the frequency of some forms of cancer, type II diabetes, atherosclerosis, and ischemic heart disease (Hinson and Raven). As is the case with estrogen and testosterone, DHEA has been and is being used in HRT, frequently in uncontrolled circumstances by the public at large in the United States. Although data from animal studies indicate that DHEA supplementation can counter some age-related changes (e.g., in immune function), the results on healthy, older humans leave the question of benefit in doubt (Svec and Porter). However, DHEA may be of help in some medical conditions, including serum lupus erythematosis and serious depression. No adverse effects have been reported.

No discussion of hormones and aging would be complete without consideration of human growth hormone (HGH) and insulin-like growth factor-1 (IGF-1). HGH is produced by the pituitary and affects target tissues principally through a mediating hormone/cytokine, IGF-1, that is synthesized in peripheral tissue. HGH and IGF-1 are potent anabolic agents capable of stimulating cell proliferation and protein synthesis, and recombinant HGH is the intervention of choice for treating individuals with short stature and adult HGH deficiency. HGH and IGF-1 levels decline with age (somatopause ) (Vermeulen), and HGH and HGH secretagogue therapy have emerged as strategies for helping the frail elderly regain strength and muscle mass. However, as is the case with testosterone, it remains to be seen whether the benefits of such an approach outweigh the risks to the individuals, including peripheral edema and a decrease in insulin sensitivity (Cummings and Merriam). Ironically, recent data show that dwarf mice with growth hormone deficiency and, as a consequence, reduced body size live longer than their normal littermates.

Arnold Kahn

See also Androgen; Andropause; Biomarkers; DHEA; Estrogen; Growth Hormone; Insulin; Longevity, Reproduction; Menopause; Neuroendocrine System; Theories of Biological Aging: Disposable Soma.

BIBLIOGRAPHY

Bain, J. "Andropause. Testosterone Replacement Therapy for Aging Men." Canadian Family Physician 47 (2001): 91–97.

Cummings, D. E., and Merriam, G. R. "Age-Related Changes in Growth Hormone: Should the Somatopause Be Treated?" Seminar in Reproductive Endocrinology 17, no. 4 (1999): 311–325.

Gosden, R. Cheating Time: Science, Sex and Aging. New York: W. H. Freeman, 1996.

Hinson, J. P., and Raven, P. W. "DHEA Deficiency Syndrome: A New Term for Old Age?" Journal of Endocrinology 163 (1999): 1–5.

Kirkwood, B. L. "Evolution of Aging." Nature 270 (1977): 301–304.

Palacios, S. "Current Perspectives on the Benefits of HRT in Menopausal Women." Maturitas 33, supp. 1 (November 1999): S1–S13.

Perry, H. M., III "The Endocrinology of Aging." Clinical Chemistry 45, no. 8 (pt 2) (1999): 1369–1376.

Rose, M. R. Evolutionary Biology of Aging. New York: Oxford University Press, 1991.

Svec, F., and Porter, J. R. "The Actions of Exogenous Dehydroepiandrosterone in Experimental Animals and Humans." Proceedings of the Society for Experimental Biology and Medicine 218 (1997): 174–191.

Vermeulen, A. "Andropause." Maturitas 34, no. 1 (2000): 5–15.