Endocrine system

Major endocrine glands. (Male left, female on the right.) 1. Pineal gland 2. Pituitary gland 3. Thyroid gland 4. Thymus 5. Adrenal gland 6. Pancreas 7. Ovary 8. Testes

The endocrine system, which is found in vertebrates, is a control system of ductless glands and single cells that secrete chemical messengers called hormones. These hormones pass directly from the glands into the body and are transmitted through the blood or via diffusion, rather than being secreted through tubes. The endocrine system provides a multitude of functions, including influencing growth and development, mood, metabolism, and sexual reproduction.

The endocrine system consists of three main components: endocrine glands, hormones, and target cells.

In humans, there are eight main glands that generally are considered part of the endocrine system: adrenal gland, pituitary gland, hypothalamus, pancreas, thyroid gland, pineal gland, parathyroid gland, and the reproductive glands, ovaries in women and testes in men. Other organs of the body also produce and secrete hormones, but are generally not considered part of the endocrine system; these include the heart, kidney, liver, thymus, skin, and placenta. Sometimes the thymus gland and the kidney are included as part of the endocrine system, and the pineal gland sometimes is not included.

The endocrine system does not include exocrine glands such as the salivary glands, sweat glands, and glands within the gastrointestinal tract. Exocrine glands release their secretions through ducts into the external environment (Silverthorn 2004). The pancreas, however, has both an endocrine function, in releasing hormones, and an exocrine function, in releasing digestive enzymes.

The endocrine system's incredible complexity and sensitivity reveals the exceptional harmony within biological systems. Hormones produced in one part of the body enter the blood stream and effect specific receptors in another portion of the body. Each component of the system works together in producing the hormone, distributing it, and regulating its concentration. This complexity is sometimes cited as evidence of intelligent design; however, other researchers have used molecular studies to trace the evolution of vertebrate steroid hormones from hundreds of millions of years ago (Bridgham, Carroll, and Thorton 2006). Significantly, present-day pollutants, such as PVC, can interfere with hormones and disrupt this sensitive system.

Overview

Hormones produced by the endocrine system affect most cells and systems in the body. Whereas the nervous system controls body processes that require rapid responses, the endocrine system influences body processes that happen slowly. Hormones regulate cell growth, development of the body, metabolism, tissue function, sexual development, and reproduction.

Hormones

Hormones are often divided into three main groups according to their chemical makeup: peptide/ protein hormones containing three or more amino acids; steroid hormones derived from cholesterol; and amine hormones derived from one amino acid (Silverthorn 2004).

Hormones are secreted directly into the blood by endocrine glands, which are mostly of mesodermal or entodermal origin (Wyngaarden 1982). As hormones travel through the blood, they are transported to various tissues and organs, whose cells are collectively called target cells. Because hormones function by binding to receptors, only cells having the appropriate receptor for a hormone can respond to the message being carried by that hormone. Hormones can execute their effect at minimum concentrations and their action is terminated either through degradation in the blood or by endocytosis of the receptor-hormone complex. The rate of degradation in the blood refers to a hormone's half life.

Hormones In Action

The endocrine system depends heavily upon the action of hormones, which are released according to one or more of the following types of influences:

• Spontaneous release at a constant rate or under circadian rhythm
• Various physiological or pathological stimuli
• "Sensor" mechanisms that monitor hormone levels and their suitability to the body's needs (Wyngaarden 1982)

Once hormones are released into the blood, they act upon their target cells by binding to receptors and initiating biochemical responses, known as the cellular mechanism of action of the hormone (Silverthorn 2004). These responses can vary from tissue to tissue and not all cells may respond to a specific hormone. At times, however, one hormone can act on multiple tissues at once. A hormone can also stimulate or inhibit the release of other hormones, in which case it is called a tropic hormone. The anterior pituitary and hypothalamus release several such hormones.

It is not uncommon for more than one hormone to be released at the same time. In such cases, different types of hormone interactions can occur. If the hormones yield a result that is more than additive, a synergistic interaction is said to have taken place. Conversely, if one hormone counteracts the action of another hormone, they are said to be antagonistic to one another. A permissive interaction can occur if one hormone is needed for a second hormone to fully exert its effects. In this situation, the first hormone is said to be permissive to the second one.

The three major groups of hormones—peptide/protein hormones, steroid hormones, and amine hormones—each share several similarities as well as several differences.

Peptide hormones are made and stored in vesicles within cells until they receive a signal for secretion. Initially, peptide hormones are made as preprohormones, which are inactive, and then are converted into prohormones. These prohormones are then cut into active hormones and peptide pieces, which are all secreted together. Because of their hydrophilic (water loving) nature, peptide hormones travel freely in the blood as they dissolve. They experience short half lives and tend to bind to surface cell receptors to initiate quick cellular responses. Peptide hormones can cause the synthesis of new proteins.

Steroid hormones, on the other hand, are made on demand. Because they are derived from cholesterol, they are hydrophobic (water fearing) and tend to travel in the blood with protein carriers. Consequently, they have a longer half life. Receptors for steroid hormones are traditionally found inside the target cell. Responses include the turning on and off of genes and the direct synthesis of fresh proteins. Overall, the cell responses with steroid hormones are slower than those with peptide hormones.

Amine hormones are those that are derived from a single amino acid. They can behave like a peptide hormone or as a combination of a peptide hormone and steroid hormone.

Regulation of hormone release and concentration

After a hormone has been secreted and has exerted its effect, its action must be terminated. This is accomplished by enzymes, which degrade, or breakdown, the hormone into metabolites. The metabolites are excreted along with bile and/or urine. Enzymes may be present in the blood or within the cell itself. Endocytosis of the receptor-hormone complex can also terminate hormone action. As noted above, the rate at which a hormone is broken down in the bloodstream is called the half life of the hormone. It is the amount of time needed to reduce the hormone concentration by one-half. This rate gives a measure of the period of time a hormone is active in the body.

The endocrine system regulates hormone release and concentration through the negative feedback loop. Increases in hormone activity decrease the production and secretion of that hormone. Similarly, a decrease in activity of a hormone prompts an increase in the production and release of that hormone. The immune system as well as other factors contribute as control factors of hormone secretion. Together, these various mechanisms of control regulate the levels of hormones within the body.

The endocrine system works in close relation with the nervous system. It links the brain to the organs that control various aspects of the body. In addition, neurohormones are released by specialized groups of neurons in the brain. These function similarly to hormones and are often categorized into three major groups: catecholamines; hypothalamic neurohormones that monitor hormone release from the anterior pituitary; and hypothalamic neurohormones that monitor hormone release from the posterior pituitary. Neuroendocrinology is an area of medicine that focuses on the overlapping fields between the nervous and endocrine systems.

Major endocrine glands in human body

The human body contains several endocrine glands and cells that secrete hormones which carry out certain functions. The main glands are the pineal gland, hypothalamus, pituitary gland, thyroid gland, parathyroid gland, adrenal gland, pancreas, and the reproductive glands (ovaries in women and testes in men).

Pineal gland

The pineal gland is located deep in the brain. It secretes melatonin, which is known as the "darkness hormone" because it is secreted at night while we sleep. The body's circadian rhythm, or light-dark cycles, are dependent on the levels of melatonin in the blood. The hormone is classified as an amine hormone derived from tryptophan (amino acid). The specific target of melatonin is unclear. Hormones released:

• Melatonin

Hypothalamus

The hypothalamus, a cluster of neurons found in the brain, controls the body's homeostasis and behavioral drives, such as thirst and food intake. The hypothalamus secretes trophic hormones that control the release of other hormones in the pituitary gland, specifically in the anterior pituitary. The trophic hormones released by the hypothalamus include:

• Prolactin-releasing hormone (PRH)
• Prolactin-inhibiting hormone (PIH; dopamine)
• Thyrotropin-releasing hormone (TRH)
• Corticotropin-releasing hormone (CRH)
• Growth hormone-inhibiting hormone (GHIH; somatostatin)
• Growth hormone-releasing hormone (GHRH)
• Gonadotropin-releasing hormone (GnRH)

Once released, these hormones, which are present in both males and females, travel to the anterior pituitary through the hypothalamic-hypophyseal portal system and either stimulate or inhibit the release of the hormones of the anterior pituitary gland.

Anterior Pituitary

The anterior pituitary is located in the brain and is part of the larger pituitary gland. It secretes six peptide hormones (in both sexes), all of which are controlled by the trophic hormones of the hypothalamus.

• Prolactin controls milk production in the breast
• Thyroid-stimulating hormone (TSH; thyrotropin) acts on the thyroid gland as a trophic hormone
• Adrenocorticotropic hormone (ACTH; corticotropin) targets the adrenal cortex and affects the release of cortisol
• Growth hormone (GH; somatotrophin) targets the liver, consequently affecting the release of insulin-like growth factors (IGFs); also targets several other tissues
• Follicle-stimulating hormone (FSH)- acts upon the endocrine cells of the gonads in both males and females; also affects germ cells of the gonads
• Luteinizing hormone (LH) acts upon the endocrine cells of the gonads in both males and females; also affects germ cells of the gonads

Posterior Pituitary

The posterior pituitary is an extension of hypothalamic neurons and is part of the larger pituitary gland. It does not make any hormones. Rather, it stores two peptide hormones, which are made in the hypothalamus and kept for storage in the posterior pituitary. Both hormones consist of nine amino acids each (Silverthorn 2004). They are released when an electrical signal from the hypothalamus passes to the posterior pituitary causing the storage vesicles to be let into the blood circulation.

• Arginine vasopressin (AVP; also called antidiuretic hormone, ADH) targets kidney to control water balance in body
• Oxytocin (OT)- In females, acts on breast and uterus to affect milk ejection, smooth muscle contractions during labor and delivery, may play a part in controlling maternal behavior; in males, secreted from the testes and possibly other reproductive tissues, pulses of oxytocin release can be detected during ejaculation, may play a part in sperm transport within the male reproductive system (Bowen 1998).

Thyroid gland

The thyroid gland, located in the neck, produces the thyroid hormones, which are amines consisting of tyrosine (an amino acid) and iodine. It also produces calcitonin, which is a peptide hormone. The thyroid hormones are not necessary for survival in adults; however, they play a crucial role for the growth and development of children. All three hormones are present in both sexes.

• Calcitonin (CT) targets bone and decreases plasma calcium levels by increasing bone formation; plays larger role in lower animals
• Thyroid hormones
  • Triiodothyronine (T3), a potent form of thyroid hormone, affects metabolism, growth and development
  • Thyroxine (T4) is a less active form of thyroid hormone that is converted into T3

Parathyroid Gland

The parathyroid gland consists of four smaller glands located on the dorsal side of the thyroid gland. It secretes one peptide hormone that plays an active role in humans, both male and female. The parathyroid gland is essential for life.

• Parathyroid hormone (PTH) acts upon bone and kidneys to increase plasma calcium levels and increase phosphate excretion

Pancreas

The pancreas is a gland that secretes several peptide hormones. They target many tissues and affect metabolism of glucose and other nutrients.

• Insulin decreases blood glucose levels, and is antagonistic to glucagon
• Glucagon increases blood glucose levels, and is antagonistic to insulin
• Somatostatin (SS), always an inhibitory hormone, stops the release of growth hormone (if released from hypothalamus) and inhibits gastrin secretion (if secreted from pancreas)
• Pancreatic polypeptide is responsible for coordinating exocrine and islet enzyme release

Adrenal Cortex

The adrenal cortex is the outer portion of the adrenal gland and it secretes steroids. It is composed of three layers: zona reticularis, zona fasciculata, and zona glomerulosa. Each layer secretes certain hormones.

• Aldosterone, one of several mineralcorticoids secreted by the zona glomerulosa (outer most layer), targets the kidney and effects sodium and potassium homeostasis in the body
• Cortisol, secreted by the zona fasciculata (middle layer) as one of many glucocorticoids, targets many tissues and causes an increase in plasma glucose levels as well as decreased immune activity. It is permissive for glucagon and catecholamines and antagonistic to insulin. It is known as the stress hormone (stress stimulus for release), and is also released according to circadian rhythm. It has a half life of 60 to 90 minutes.
• Androgens, secreted by the zona reticularis (inner-most layer), is part of the sex hormones and targets many tissues and is responsible for sex drive in females.

Adrenal Medulla

The adrenal medulla is the inner portion of the adrenal gland. It secretes catecholamines, which are classified as amine hormones. They target many tissues and are involved in the fight or flight response, or the acute stress response, of the body. This response takes over during short-term stress situations.

• Epinephrine (E; also called adrenaline) increases heart rate and stroke volume, dilates the pupils, constricts arterioles in the skin and gut while dilating arterioles in leg muscles, elevates the blood sugar level, begins the breakdown of lipids in adipocytes, and exhibits a suppressive effect on the immune system.
• Norepinephrine (NE; also called noradrenaline) increases heart rate, releases energy from fat, increases muscle readiness, and is recognized as playing a large role in attention and focus. Changes in the NE system are implicated in depression. NE is also a neurotransmitter in the brain.

Testes

The testes, or testicles, are the male gonads (reproductive organs) that play a crucial role in sexual development, secondary sex characteristics, and sperm production. These glands (two testicles) are located outside of the male body and are not fully developed until after puberty, which occurs in adolescence.

• Androgen, a steroid hormone that targets many tissues, plays primary role in sperm production and development of secondary sexual characteristics.
• Inhibin, a peptide hormone, inhibits the release of follicle stimulating hormone (FSH) from the anterior pituitary.

Ovaries

The female reproductive organ is the ovary. Each female is born with two ovaries, although living with one is possible and common. Each ovary fulfills two important functions: produce eggs and secrete hormones. Females are born with all of their eggs, which mature during the period of puberty.

• Estrogens and Progestone (P), steroid hormones that target many tissues, are involved in egg production and secondary sexual characteristics.
• Ovarian inhibin, a peptide hormone that inhibits follicle-stimulating hormone (FSH), targets the anterior pituitary.

Other hormone excreting organs

Thymus gland

The thymus gland is the site for lymphocyte (white blood cell) production. It is an immune tissue located in the chest of both sexes. Two peptide hormones are produced and secreted there, both which target lymphocytes and aid in their development.

• Thymosin
• Thymopoietin

Kidney

The human body contains two kidneys, symmetrically located in the posterior region of the abdominal cavity. The adrenal glands sit above the kidneys. In general, humans are able to live with only one kidney. Two important hormones are released from this organ in both males and females.

• Erythropoietin (EPO), a peptide hormone, targets bone marrow and is involved in red blood cell production.
• 1,25 Dihydroxy-vitamin D3 (also known as Calciferol), active form of Vitamin D3, is a steroid hormone that increases calcium absorption and targets intestines.

Heart

The heart, a major organ of the body and pump of the circulation system, releases one peptide hormone, atrial natriuretic peptide hormone. Its release from atrial myocytes, located in the atria, is stimulated by high blood pressure, atrial distention and stretching, sympathetic stimulation of β-adrenoceptors, raised sodium concentration, angiotensin-II, and endothelin (a potent vasodilator). The hormone is a 28 amino acid peptide with a 17 amino acid ring.

• Atrial Natriuretic peptide hormone (ANP; also called atriopeptin) targets kidneys and increases sodium and water excretion in order to reduce blood pressure, reduces aldosterone production by the adrenal cortex, and relaxes vascular smooth muscle in arterioles and venules.

Liver

The liver is responsible for the release of the peptid hormone angiotensinogen and also for the secretion of the peptide hormones referred to as insulin-like growth factors. The former consists of 453 amino acid residues and is cleaved to form angiotensin, which is the active form of the hormone.

• Angiotensinogen/ Angiotensin targets the adrenal cortex, brain, and blood vessels; main effects include aldosterone secretion, vasoconstriction, and increased blood pressure.
• Insulin-like growth factors (IGFs) act on many tissues and are involved in growth.

Stomach and Small Intestine

The cells of the stomach and small intestine mostly secrete hormones that aid in digestion and also cause the absorption of nutrients. They are classified as peptide hormones and target mostly the gastrointestinal tract and pancreas. The major hormones secreted are:

• Gastrin, secreted by G cells of the stomach, stimulates the release of gastric acid. Its release is inhibited by somatostatin and a pH < 1.5 (Silverthorn 2004), and the stimulus for release include amino acids in the lumen and acetylcholine in nervous reflexes.
• Cholecystokinin (CCK), secreted by intestinal cells and neurons of the brain and gut, targets gallbladder, pancreas, and stomach smooth muscles. The stimulus for release is fatty acids in the digestive system, and it excites the gallbladder for contraction and release of bile, stimulates pancreatic enzyme secretion, and stimulates satiety.
• Secretin, released by the small intestine, targets the stomach and pancreas, causes bicarbonate secretion and pepsin secretion, and inhibits gastric acid release. A stimulus for release is acid in the small intestine, while release inhibited by somatostatin.
• Gastric inhibitory peptide (GIP), secreted in small intestine, stimulates insulin release and inhibits acid secretion.
• Motilin, secreted in the small intestine, stimulates the migrating motor complex. The stimulus for release is fasting.
• Glucagon-like Peptide 1 (GLP-1), released by the small intestine, causes insulin release while inhibiting glucagon release, and may act in conjunction with GIP.
• Ghrelin, secreted by the stomach, increases the release of gastric hormone, and causes increase in food intake.

Skin

The skin is a collection of cells that serves as a protection layer in humans. Although it does not secrete hormones per se, like other organs, it does contain an intermediate form of an important hormone. The cells of the skin contain Vitamin D3, which is the precursor of 1,25 dihydroxy-vitamin D3, or calciferol. Vitamin D3 is converted into its active form by the sun.

• Vitamin D3

Adipose tissue

Adipose tissue, which is made up of adipocyte cells, stores energy in the form of fat. It also provides insulation for the body. It primarily secretes a peptide hormone called leptin, which circulates in the blood at levels proportional to body fat. It also secretes several other hormones including estradiol.

• Leptin targets hypothalamus and other tissues and is involved in regulating food intake, metabolism, and reproduction.
• Estradiol (E2), a steroid sex hormone produced by aromatase (found in adipose tissue in both males and females), has a critical impact on reproductive and sexual functioning as well as on other organs including bone structure. It represents the major estrogen in humans.
• Resistin targets several tissues in the body; its exact function is not known.
• Adiponectin is a peptide hormone that modulates a number of metabolic processes, including glucose regulation and fatty acid catabolism. Levels of the hormone are inversely correlated with body mass index (BMI). It plays a role in metabolic disorders, such as type 2 diabetes, obesity, and atherosclerosis.

Placenta

Although not usually thought of as a gland, the placenta does secrete hormones. It is present only in pregnant females. Nutrient and gas transfer between the mother and fetus occurs through the placenta. The placenta also serves as a barrier and attempts to filter out harmful substances before they are able to pass on to the fetus.

• Estrogens and progesterone (P), steroid hormones needed to maintain the pregnancy, target many tissues and cause fetus and maternal development.
• Human chorionic somatomammotropin (CS; also called human placental lactogen, or HPL), a peptide hormone, is involved in metabolism and increases levels of glucose and fats in mother's blood. It targets many tissues.
• Chorionic gonadotropin (CG) is a peptide hormone that specifically targets the corpus luteum of the ovary to cause the release of various hormones.
• Human chorionic gonadotropin (hCG), a peptide hormone, prevents the disintegration of the corpus luteum of the ovary and thereby maintains progesterone production (critical for pregnancy in humans).

Ovarian follicle and Corpus luteum

In females, the ovarian follicle and corpus luteum each secrete estrogens, mainly estradiol, and progesterone. These aid in egg maturation and prepare for implantation of the egg into the endometrium of the uterus.

Role in disease

The field of medicine that deals with disorders of the endocrine glands is endocrinology, a branch of the larger field of internal medicine. Diseases of the endocrine system are common and can result when the sensitivity of target cells to hormones has varied. Other causes of endocrinopathies include hyper or hypo secretion of hormone, ectopic production of hormone, or iatrogenic factors (physician induced). Some common pathologies include diabetes mellitus and thyroid disease.

Endocrinopathies are classified as primary, secondary, or tertiary. Primary is target cell dysfunction and is normally associated with increased or decreased secretory hormones. Secondary refers to a dysfunction that originates elsewhere, like the pituitary gland, and is normally associated with increased or decreased production of trophic hormones. Tertiary is associated with dysfunction of the hypothalamus and its releasing hormones.

Diffuse endocrine system

Organs are not the sole way for hormones to be released into the body; there are a host of specific cells that secrete hormones independently. These are called the diffuse endocrine system and include myocytes in the atria of the heart and epithelial cells in the stomach and small intestine. In fact, if one were to classify any chemical excretions by the term "hormone," every cell in the human body could be considered a part of the endocrine system.

References

ISBN links support NWE through referral fees

• Bowen, R. 1998. Oxytocin. Colorado State University. http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/hypopit/oxytocin.html
• Bridgham, J. T., S. M. Carroll, and J. W. Thornton. 2006. Evolution of Hormone-Receptor Complexity by Molecular Exploitation. Science 312: 97-101.
• Silverthorn, D. 2004. Human Physiology, An Integrated Approach (3rd Edition). San Francisco, CA: Benjamin Cummings. ISBN 0131020153
• Wyngaarden, J. B., and L. H. Smith. 1982. Cecil Textbook of Medicine (16th Edition). Philadelphia, PA: W. B. Saunders Company. ISBN 072169621X

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