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

The Gale Encyclopedia of Science