Hormone

For other uses, see Hormone (disambiguation).

Epinephrine (adrenaline), a catecholamine-type hormone

A hormone (from Greek ὁρμή, "impetus") is a class of regulatory biochemicals produced in all multicellular organisms by glands, and transported by the circulatory system to a distant target organ to coordinate its physiology and behavior. Hormones act by binding to specific receptors in the target organ. Hormones regulate a variety of physiological and behavioral activities, including digestion, metabolism, respiration, tissue function, sensory perception, sleep, excretion, lactation, stress, growth and development, movement, reproduction, and mood. Hormones rarely change the function of a cell; rather, they alter the rate of normal cellular function which can influence cell morphology and size (including development of muscle and neuronal cells), and affect cell death (apoptosis). Generally, only a small amount of hormone is required to alter cell metabolism. Hormones have many different functions and modes of action; one hormone may have several effects on different target organs, and, conversely, one target organ may be affected by more than one hormone.

The popular belief that individual differences in behavior reflects differences in hormone concentrations is not necessarily true. Individual differences in behavior can reflect hormone concentrations, pattern of hormone release, numbers and location of hormone receptors, and the efficiency of those receptors in affecting gene transcription. Although hormones undoubtedly affect behavior, it is also true that behavior can influence hormonal levels and hormonal effects. In fact, behavior often does affect hormone levels which in turn influences subsequent behavior. There are classes of evidence for determining hormone-behavior interactions: (1) A hormonally-dependent behavior should disappear when the hormonal source is removed or actions of the hormone are blocked; (2) After the behavior stops, restoration of the missing source or its hormone should reinstate the absent behavior; (3) Hormone concentrations and the behavior should covary; in practice, the behavior should be observed when concentrations are relatively high and never or rarely observed when concentrations are low (3rd class of evidence is particularly difficult to obtain since many hormones have a long latency of action (due to up-regulation) and/or a long offset latency (due to down-regulation)) .

Hormones are similar to neurotransmitters, but can operate over a greater distance and over a much greater temporal range than neurotransmitters. There are various distinctions between hormones and neurotransmitters: (1) Neural messages can only travel along existing nerve tracts, while hormonal messages can travel in the circulatory system which allows any cell in contact with blood the opportunity to receive a message; (2) Neural messages are all-or-none events that have rapid onset and offset (can occur in milliseconds and travel at speeds up to 100 meters per second), whereas neural signals are analog, graded events that can take seconds, minutes or hours to take place.

The endocrine system secretes hormones directly into the circulatory system typically into fenestrated capillaries, whereas the exocrine system secretes its hormones indirectly using ducts. Hormones with paracrine function diffuse through the interstitial spaces to nearby target tissues. Cells respond to a hormone when they express a specific receptor for that hormone. The hormone binds to the receptor protein, resulting in the activation of a signal transduction mechanism. This ultimately leads to cell type-specific genomic response whereby the hormone activates genes that regulate protein synthesis (e.g., up-regulation: synthesis of a receptor for that hormone). Some hormone effects are nongenomic (transcription-independent) whereby they are characterized by their insensitivity to inhibitors or transcription and protein synthesis.

Plant hormones are known as phytohormones. In animals, the brain is often a target organ for many of these hormones, and the brain, in turn, regulates the secretion of these hormones.

A variety of exogenous chemical compounds, both natural and synthetic, have hormone-like effects on both humans and wildlife. Their interference with the synthesis, secretion, transport, binding, action, or elimination of natural hormones in the body can change the homeostasis, reproduction, development, and/or behavior, just as endogenously produced hormones do.

Endocrinology is a branch of science concerned with the biosynthesis, storage, chemistry, biochemical and physiological function of hormones and with the cells of the endocrine glands and tissues that secrete them.

Hormones as signals

See also Signal transduction.

Hormonal signaling involves the following:

1. Biosynthesis of a particular hormone in a particular tissue
2. Storage and secretion of the hormone
3. Transport of the hormone to the target cell(s)
4. Recognition of the hormone by an associated cell membrane or intracellular receptor protein
5. Relay and amplification of the received hormonal signal via a signal transduction process: This then leads to a cellular response. The reaction of the target cells may then be recognized by the original hormone-producing cells, leading to a down-regulation in hormone production. This is an example of a homeostatic negative feedback loop.
6. Degradation of the hormone.

Hormone cells are typically of a specialized cell type, residing within a particular endocrine gland, such as thyroid gland, ovaries, and testes. Hormones exit their cell of origin via exocytosis or another means of membrane transport. The hierarchical model is an oversimplification of the hormonal signaling process. Cellular recipients of a particular hormonal signal may be one of several cell types that reside within a number of different tissues, as is the case for insulin, which triggers a diverse range of systemic physiological effects. Different tissue types may also respond differently to the same hormonal signal. Because of this, hormonal signaling is elaborate and hard to dissect.

Interactions with receptors

The left diagram shows a steroid (lipid) hormone (1) entering a cell and (2) binding to a receptor protein in the nucleus, causing (3) mRNA synthesis which is the first step of protein synthesis. The right side shows protein hormones (1) binding with receptors which (2) begins a transduction pathway. The transduction pathway ends (3) with transcription factors being activated in the nucleus, and protein synthesis beginning. In both diagrams, a is the hormone, b is the cell membrane, c is the cytoplasm, and d is the nucleus.

Most hormones initiate a cellular response by initially combining with either a specific intracellular or cell membrane associated receptor protein. A cell may have several different receptors that recognize the same hormone and activate different signal transduction pathways, or a cell may have several different receptors that recognize different hormones and activate the same biochemical pathway.

For many hormones, including most protein hormones, the receptor is membrane-associated and embedded in the plasma membrane at the surface of the cell. The interaction of hormone and receptor typically triggers a cascade of secondary effects within the cytoplasm of the cell, often involving phosphorylation or dephosphorylation of various other cytoplasmic proteins, changes in ion channel permeability, or increased concentrations of intracellular molecules that may act as secondary messengers (e.g., cyclic AMP). Some protein hormones also interact with intracellular receptors located in the cytoplasm or nucleus by an intracrine mechanism.

For hormones such as steroid or thyroid hormones, their receptors are located intracellularly within the cytoplasm of their target cell. To bind their receptors, these hormones must cross the cell membrane. They can do so because they are lipid-soluble. The combined hormone-receptor complex then moves across the nuclear membrane into the nucleus of the cell, where it binds to specific DNA sequences, effectively amplifying or suppressing the action of certain genes, and affecting protein synthesis. However, it has been shown that not all steroid receptors are located intracellularly. Some are associated with the plasma membrane.

An important consideration, dictating the level at which cellular signal transduction pathways are activated in response to a hormonal signal, is the effective concentration of hormone-receptor complexes that are formed. Hormone-receptor complex concentrations are effectively determined by three factors:

1. The number of hormone molecules available for complex formation
2. The number of receptor molecules available for complex formation
3. The binding affinity between hormone and receptor.

The number of hormone molecules available for complex formation is usually the key factor in determining the level at which signal transduction pathways are activated, the number of hormone molecules available being determined by the concentration of circulating hormone, which is in turn influenced by the level and rate at which they are secreted by biosynthetic cells. The number of receptors at the cell surface of the receiving cell can also be varied, as can the affinity between the hormone and its receptor. Estrogen metabolites generally have much lower receptor affinity than the parent hormone.

Physiology of hormones

Most cells are capable of producing one or more molecules, which act as signaling molecules to other cells, altering their growth, function, or metabolism. The classical hormones produced by cells in the endocrine glands mentioned so far in this article are cellular products, specialized to serve as regulators at the overall organism level. However, they may also exert their effects solely within the tissue in which they are produced and originally released.

The rate of hormone biosynthesis and secretion is often regulated by a homeostatic negative feedback control mechanism. Such a mechanism depends on factors that influence the metabolism and excretion of hormones. Thus, higher hormone concentration alone cannot trigger the negative feedback mechanism. Negative feedback must be triggered by overproduction of an "effect" of the hormone.

Hormone secretion can be stimulated and inhibited by:

• Other hormones (stimulating- or releasing -hormones)
• Plasma concentrations of ions or nutrients, as well as binding globulins
• Neurons and mental activity
• Environmental changes, e.g., of light or temperature

One special group of hormones is the tropic hormones that stimulate the hormone production of other endocrine glands. For example, thyroid-stimulating hormone (TSH) causes growth and increased activity of another endocrine gland, the thyroid, which increases output of thyroid hormones.

A recently identified class of hormones is that of the "hunger hormones" - ghrelin, orexin, and PYY 3-36 - and "satiety hormones" - e.g., cholecystokinin, leptin, nesfatin-1, obestatin.

To release active hormones quickly into the circulation, hormone biosynthetic cells may produce and store biologically inactive hormones in the form of pre- or prohormones. These can then be quickly converted into their active hormone form in response to a particular stimulus.

Eicosanoids are considered to act as local hormones.

Effects of hormones

In mammals

Hormones have the following effects on the body:

• stimulation or inhibition of growth
• wake-sleep cycle and other circadian rhythms
• mood swings
• induction or suppression of apoptosis (programmed cell death)
• activation or inhibition of the immune system
• regulation of metabolism
• preparation of the body for mating, fighting, fleeing, and other activity
• preparation of the body for a new phase of life, such as puberty, parenting, and menopause
• control of the reproductive cycle
• hunger cravings
• sexual arousal

A hormone may also regulate the production and release of other hormones. Hormone signals control the internal environment of the body through homeostasis.

Chemical classes of hormones

As hormones are defined functionally, not structurally, they may have diverse chemical structures. Hormones occur in multicellular organisms (plants, animals, fungi, brown algae and red algae). These compounds occur also in unicellular organisms, and may act as signaling molecules, but there is no consensus if, in this case, they can be called hormones.

Animals

Vertebrate hormones fall into three chemical classes:

• Peptide hormones consist of chains of amino acids. Examples of small peptide hormones are TRH and vasopressin. Peptides composed of scores or hundreds of amino acids are referred to as proteins. Examples of protein hormones include insulin and growth hormone. More complex protein hormones bear carbohydrate side-chains and are called glycoprotein hormones. Luteinizing hormone, follicle-stimulating hormone and thyroid-stimulating hormone are glycoprotein hormones. There is also another type of hydrophilic hormone called nonpeptide hormones. Although they don't have peptide connections, they are assimilated as peptide hormones.
• Lipid and phospholipid-derived hormones derive from lipids such as linoleic acid and arachidonic acid and phospholipids. The main classes are the steroid hormones that derive from cholesterol and the eicosanoids. Examples of steroid hormones are testosterone and cortisol. Sterol hormones such as calcitriol are a homologous system. The adrenal cortex and the gonads are primary sources of steroid hormones. Examples of eicosanoids are the widely studied prostaglandins and Lipoxins.
• Monoamines derived from aromatic amino acids like phenylalanine, tyrosine, tryptophan by the action of aromatic amino acid decarboxylase enzymes.

Those classes of hormones are found too in other groups of animals. In insects and crustaceans, there is a hormone with an unusual chemical structure, compared with other animal hormones, the juvenile hormone, a sesquiterpenoid.

Plants

Further information: Plant hormone § Classes of plant hormones

Pharmacology

Many hormones and their analogues are used as medication. The most commonly prescribed hormones are estrogens and progestagens (as methods of hormonal contraception and as HRT), thyroxine (as levothyroxine, for hypothyroidism) and steroids (for autoimmune diseases and several respiratory disorders). Insulin is used by many diabetics. Local preparations for use in otolaryngology often contain pharmacologic equivalents of adrenaline, while steroid and vitamin D creams are used extensively in dermatological practice.

A "pharmacologic dose" or "supraphysiological dose" of a hormone is a medical usage referring to an amount of a hormone far greater than naturally occurs in a healthy body. The effects of pharmacologic doses of hormones may be different from responses to naturally occurring amounts and may be therapeutically useful, though not without potentially adverse side effects. An example is the ability of pharmacologic doses of glucocorticoids to suppress inflammation.

Important human hormones

See: List of human hormones

See also

• Autocrine signaling
• Cytokine
• Endocrine system
• Endocrinology
• Growth factor
• Hormone disruptor
• Intracrine
• Metabolomics
• Neuroendocrinology
• Paracrine signaling
• Plant hormones or plant growth regulators
• Semiochemical
• Sexual motivation and hormones

External links

• The Hormone Foundation
• Article on hormones and their receptors
• HMRbase: A database of hormones and their receptors
• Hormones at the U.S. National Library of Medicine Medical Subject Headings (MeSH)