Hormones affect distant cells by binding to specificreceptor proteins in the target cell, resulting in a change in cell function. When a hormone binds to the receptor, it results in the activation of asignal transduction pathway that typically activates genetranscription, resulting in increasedexpression of targetproteins. Hormones can also act in non-genomic pathways that synergize with genomic effects.[6] Water-soluble hormones (such as peptides and amines) generally act on the surface of target cells viasecond messengers. Lipid soluble hormones, (such assteroids) generally pass through the plasma membranes of target cells (bothcytoplasmic andnuclear) to act within theirnuclei.Brassinosteroids, a type of polyhydroxysteroids, are a sixth class of plant hormones and may be useful as an anticancer drug for endocrine-responsive tumors to causeapoptosis and limit plant growth. Despite being lipid soluble, they nevertheless attach to their receptor at the cell surface.[7]
In vertebrates,endocrine glands are specialized organs thatsecrete hormones into theendocrine signaling system. Hormone secretion occurs in response to specific biochemical signals and is often subject tonegative feedback regulation. For instance, highblood sugar (serum glucose concentration) promotesinsulin synthesis. Insulin then acts to reduce glucose levels and maintainhomeostasis, leading to reduced insulin levels. Upon secretion, water-soluble hormones are readily transported through the circulatory system. Lipid-soluble hormones must bond tocarrier plasma glycoproteins (e.g.,thyroxine-binding globulin (TBG)) to formligand-protein complexes. Some hormones, such as insulin and growth hormones, can be released into the bloodstream already fully active. Other hormones, calledprohormones, must be activated in certain cells through a series of steps that are usually tightly controlled.[8] Theendocrine systemsecretes hormones directly into thebloodstream, typically viafenestrated capillaries, whereas theexocrine system secretes its hormones indirectly usingducts. Hormones withparacrine function diffuse through theinterstitial spaces to nearby target tissue.
Plants lack specialized organs for the secretion of hormones, although there is spatial distribution of hormone production. For example, the hormone auxin is produced mainly at the tips of youngleaves and in theshoot apical meristem. The lack of specialised glands means that the main site of hormone production can change throughout the life of a plant, and the site of production is dependent on the plant's age and environment.[9]
Relay and amplification of the received hormonal signal via asignal 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 adownregulation in hormone production. This is an example of ahomeostaticnegative feedback loop.
Breakdown of the hormone.
Exocytosis and other methods ofmembrane transport are used to secrete hormones when the endocrine glands are signaled. The hierarchical model is anoversimplification 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 forinsulin, which triggers a diverse range of systemic physiological effects. Different tissue types may also respond differently to the same hormonal signal.[12]
Arnold Adolph Berthold was a Germanphysiologist andzoologist, who, in 1849, had a question about the function of thetestes. He noticed in castrated roosters that they did not have the same sexual behaviors asroosters with their testes intact. He decided to run an experiment on male roosters to examine this phenomenon. He kept a group of roosters with their testes intact, and saw that they had normal sized wattles and combs (secondarysexual organs), a normal crow, and normal sexual and aggressive behaviors. He also had a group with their testes surgically removed, and noticed that their secondary sexual organs were decreased in size, had a weak crow, did not have sexual attraction towards females, and were not aggressive. He realized that this organ was essential for these behaviors, but he did not know how. To test this further, he removed one testis and placed it in the abdominal cavity. The roosters acted and had normal physicalanatomy. He was able to see that location of the testes does not matter. He then wanted to see if it was agenetic factor that was involved in the testes that provided these functions. He transplanted a testis from another rooster to a rooster with one testis removed, and saw that they had normal behavior and physical anatomy as well. Berthold determined that the location or genetic factors of the testes do not matter in relation to sexual organs and behaviors, but that somechemical in the testes being secreted is causing this phenomenon. It was later identified that this factor was the hormonetestosterone.[13][14]
Although known primarily for his work on theTheory of Evolution,Charles Darwin was also keenly interested in plants. Through the 1870s, he and his sonFrancis studied the movement of plants towards light. They were able to show that light is perceived at the tip of a young stem (thecoleoptile), whereas the bending occurs lower down the stem. They proposed that a 'transmissible substance' communicated the direction of light from the tip down to the stem. The idea of a 'transmissible substance' was initially dismissed by other plant biologists, but their work later led to the discovery of the first plant hormone.[15] In the 1920s Dutch scientistFrits Warmolt Went and Russian scientistNikolai Cholodny (working independently of each other) conclusively showed that asymmetric accumulation of a growth hormone was responsible for this bending. In 1933 this hormone was finally isolated by Kögl, Haagen-Smit and Erxleben and given the name 'auxin'.[15][16][17]
British physicianGeorge Oliver and physiologistEdward Albert Schäfer, professor at University College London, collaborated on the physiological effects of adrenal extracts. They first published their findings in two reports in 1894, a full publication followed in 1895.[18][19] Though frequently falsely attributed tosecretin, found in 1902 by Bayliss and Starling, Oliver and Schäfer's adrenal extract containingadrenaline, the substance causing the physiological changes, was the first hormone to be discovered. The term hormone would later be coined by Starling.[20]
William Bayliss andErnest Starling, aphysiologist andbiologist, respectively, wanted to see if thenervous system had an impact on thedigestive system. From the work ofMartin Heidenhain andClaude Bernard,[21] they knew that thepancreas was involved in the secretion ofdigestive fluids after the passage of food from thestomach to theintestines, which they believed to be due to the nervous system. They cut the nerves to the pancreas in an animal model and discovered that it was not nerve impulses that controlled secretion from the pancreas. It was determined that a factor secreted from the intestines into thebloodstream was stimulating the pancreas to secrete digestive fluids. This was namedsecretin: a hormone.
In 1905 Starling coined he word hormone from the Greekto arouse or excite which he defined as “thechemical messengers which speeding from cell to cell along the blood stream, may coordinate the activities and growth of different parts of the body”.[22]
Hormonal effects are dependent on where they are released, as they can be released in different manners.[23] Not all hormones are released from a cell and into the blood until it binds to a receptor on a target. The major types of hormone signaling are:
Peptide hormones are made of a chain ofamino acids that can range from just 3 to hundreds. Examples includeoxytocin andinsulin.[13] Their sequences are encoded inDNA and can be modified byalternative splicing and/orpost-translational modification.[23] They are packed in vesicles and arehydrophilic, meaning that they are soluble in water. Due to their hydrophilicity, they can only bind to receptors on the membrane, as travelling through the membrane is unlikely. However, some hormones can bind to intracellular receptors through anintracrine mechanism.
Steroid hormones are derived from cholesterol. Examples include the sex hormonesestradiol andtestosterone as well as the stress hormonecortisol.[26] Steroids contain four fused rings. They arelipophilic and hence can cross membranes to bind to intracellularnuclear 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 binding to eithercell surface receptors orintracellular receptors. A cell may have several differentreceptors that recognize the same hormone but activate differentsignal transduction pathways, or a cell may have several different receptors that recognize different hormones and activate the same biochemical pathway.[29]
Forsteroid orthyroid hormones, theirreceptors are locatedinside the cell within thecytoplasm of the target cell. These receptors belong to thenuclear receptor family of ligand-activatedtranscription factors. To bind their receptors, these hormones must first cross the cell membrane. They can do so because they are lipid-soluble. The combined hormone-receptorcomplex then moves across the nuclear membrane into the nucleus of the cell, where it binds to specificDNA sequences, regulating the expression of certaingenes, and thereby increasing the levels of the proteins encoded by these genes.[32] However, it has been shown that not all steroid receptors are located inside the cell. Some are associated with theplasma membrane.[33]
A hormone may also regulate the production and release of other hormones. Hormone signals control the internal environment of the body throughhomeostasis.
The rate of hormone biosynthesis and secretion is often regulated by ahomeostaticnegative feedback control mechanism. Such a mechanism depends on factors that influence themetabolism andexcretion 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.[35][36]
Blood glucose levels are maintained at a constant level in the body by a negative feedback mechanism. When the blood glucose level is too high, the pancreas secretes insulin and when the level is too low, the pancreas then secretes glucagon. The flat line shown represents the homeostatic set point. The sinusoidal line represents the blood glucose level.
Hormone secretion can be stimulated and inhibited by:
Other hormones (stimulating- orreleasing -hormones)
Plasma concentrations of ions or nutrients, as well as bindingglobulins
To release active hormones quickly into thecirculation, hormone biosynthetic cells may produce and store biologically inactive hormones in the form ofpre- orprohormones. These can then be quickly converted into their active hormone form in response to a particular stimulus.[37]
Eicosanoids are considered to act as local hormones. They are considered to be "local" because they possess specific effects on target cells close to their site of formation. They also have a rapid degradation cycle, making sure they do not reach distant sites within the body.[38]
Hormones are also regulated by receptor agonists. Hormones are ligands, which are any kinds of molecules that produce a signal by binding to a receptor site on a protein. Hormone effects can be inhibited, thus regulated, by competing ligands that bind to the same target receptor as the hormone in question. When a competing ligand is bound to the receptor site, the hormone is unable to bind to that site and is unable to elicit a response from the target cell. These competing ligands are called antagonists of the hormone.[39]
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 ofglucocorticoids to suppressinflammation.
At the neurological level, behavior can be inferred based on hormone concentration, which in turn are influenced by hormone-release patterns; the numbers and locations of hormone receptors; and the efficiency of hormone receptors for those involved in gene transcription. Hormone concentration does not incite behavior, as that would undermine other external stimuli; however, it influences the system by increasing the probability of a certain event to occur.[42]
Not only can hormones influence behavior, but also behavior and the environment can influence hormone concentration.[43] Thus, a feedback loop is formed, meaning behavior can affect hormone concentration, which in turn can affect behavior, which in turn can affect hormone concentration, and so on.[44] For example, hormone-behavior feedback loops are essential in providing constancy to episodic hormone secretion, as the behaviors affected by episodically secreted hormones directly prevent the continuous release of said hormones.[45]
Three broad stages of reasoning may be used to determine if a specific hormone-behavior interaction is present within a system:[46]
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 dependent hormonal source (or its types of action) is expected to bring back the absent behavior.
Though colloquially oftentimes used interchangeably, there are various clear distinctions between hormones andneurotransmitters:[47][48][39]
A hormone can perform functions over a larger spatial and temporal scale than can a neurotransmitter, which often acts in micrometer-scale distances.[49]
Hormonal signals can travel virtually anywhere in the circulatory system, whereas neural signals are restricted to pre-existingnerve tracts.[49]
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.[50]
Neural signalling is an all-or-nothing (digital) action, whereas hormonal signalling is an action that can be continuously variable as it is dependent upon hormone concentration.
Neurohormones are a type of hormone that share a commonality with neurotransmitters.[51] They are produced by endocrine cells that receive input from neurons, or neuroendocrine cells.[51] Both classic hormones and neurohormones are secreted by endocrine tissue; however, neurohormones are the result of a combination between endocrine reflexes and neural reflexes, creating a neuroendocrine pathway.[39] While endocrine pathways produce chemical signals in the form of hormones, the neuroendocrine pathway involves the electrical signals of neurons.[39] In this pathway, the result of the electrical signal produced by a neuron is the release of a chemical, which is the neurohormone.[39] Finally, like a classic hormone, the neurohormone is released into the bloodstream to reach its target.[39]
Diagram that describes hormones and their activity in the bloodstream. Hormones flow in and out of the bloodstream and are able to bind to target cells to activate the role of the hormone. This is with the help of the bloodstream flow and the secreting cell. Hormones regulate metabolism, growth and development, tissue function, sleep, reproduction, etc. The diagram also lists the important hormones in humans.
Hormone transport and the involvement of binding proteins is an essential aspect when considering the function of hormones.[52] The formation of a complex with a binding protein has several benefits: the effective half-life of the bound hormone is increased, and a reservoir of bound hormones is created, which evens the variations in concentration of unbound hormones (bound hormones will replace the unbound hormones when these are eliminated).[53] An example of the usage of hormone-binding proteins is in the thyroxine-binding protein which carries up to 80% of all thyroxine in the body, a crucial element in regulating the metabolic rate.[54]
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