Hormone

A hormone (from Greek ὁρμή, "impetus") is a class of regulatory biochemicals that is 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 serve as a major form of communication between different organs and tissues. 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. Generally, only a small amount of hormone is required to alter cell metabolism.

Hormone formation may arise at localized clusters of specific cells known as endocrine glands, or at other specialized cells with several functions. Hormone synthesis occurs in response to specific biochemical signals induced by a wide range of regulatory systems. In some cases, the rate at which these systems act on a hormone depends on the particular effect or properties of the hormone. For instance, ionized calcium concentration modulates PTH synthesis, whereas glucose concentration modulates insulin synthesis. Contrarily, regulation of hormone synthesis of gonadal, adrenal, and thyroid hormones is often dependent on a complex set of direct influences and feedback interactions involving the hypothalamic-pituitary axis (See HPA axis, HPG, HPT).

Upon secretion, certain hormones, including protein hormones and catecholamines, are water soluble and are thus readily transported through the circulatory system. On the other hand, some hormones, including steroid and thyroid hormones, are water insoluble; to allow for their widespread distribution, these hormones must bond to carrier plasma glycoproteins (e.g., throxine-binding globulin (TBG)) to form ligand-protein complexes. Some hormones are completely active when released into the bloodstream (as is the case for insulin and growth hormones), while others must be activated in specific cells through a series of activation steps that are commonly highly regulated. 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.

Hormones purposefully affect the target tissue of interest by binding to specific receptor proteins to elicit a specified action in the cellular target. Cells respond to a hormone when they express a specific receptor for that hormone. When a hormone binds to the receptor protein, it results in the activation of a signal transduction mechanism. This ultimately leads to cell type-specific genomic responses that cause the hormone to activate genes that regulate protein synthesis (e.g., up-regulation: synthesis of a receptor for that hormone).

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. 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.

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
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:

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.
 * 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.

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
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.

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.

Hormone-behavior interactions
At the neurological level, behavior can be inferred based on: hormone concentrations; hormone-release patterns; the numbers and locations of hormone receptors; and the efficiency of hormone receptors for those involved in gene transcription. Not only do hormones influence behavior, but also behavior and the environment influence hormones. Thus, a feedback loop is formed. For example, behavior can affect hormones, which in turn can affect behavior, which in turn can affect hormones, and so on.

Three broad stages of reasoning may be used when determining hormone-behavior interactions:
 * The frequency of occurrence of a hormonally-dependent behavior should correspond to that of its hormonal source
 * A hormonally-dependent behavior is not expected if the hormonal source (or its types of action) is non-existent
 * The reintroduction of a missing behaviorally-depend hormonal source (or its types of action) is expected to bring back the absent behavior

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.

Comparison with neurotransmitters
There are various clear distinctions between hormones and neurotransmitters:
 * A hormone can perform functions over a larger spatial and temporal scale than can a neurotransmitter.
 * Hormonal signals can travel virtually anywhere in the circulatory system, whereas neural signals are restricted to pre-existing nerve tracts
 * Assuming the travel distance is equivalent, neural signals can be transmitted much more quickly (in the range of milliseconds) than can hormonal signals (in the range of seconds, minutes, or hours). Neural signals can be sent at speeds up to 100 meters per second.
 * Neural signaling is an all-or-nothing (digital) action, whereas hormonal signaling is an action that can be continuously variable as dependent upon hormone concentration

Important human hormones
See: List of human hormones