Corticosterone
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Corticosterone, also known as 17-deoxycortisol and 11β,21-dihydroxyprogesterone, is a 21-carbon
steroid hormone A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into two classes: corticosteroids (typically made in the adrenal cortex, hence ''cortico-'') and sex steroids (typically made in the gonads or placenta). Withi ...
of the corticosteroid type produced in the cortex of the
adrenal gland The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex whic ...
s. It is of minor importance in humans, except in the very rare case of congenital adrenal hyperplasia due to 17α-hydroxylase deficiency.


Roles

In many species, including amphibians, reptiles, rodents and birds, corticosterone is a main
glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every verteb ...
, involved in regulation of energy, immune reactions, and
stress Stress may refer to: Science and medicine * Stress (biology), an organism's response to a stressor such as an environmental condition * Stress (linguistics), relative emphasis or prominence given to a syllable in a word, or to a word in a phrase ...
responses. However, in
humans Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...
, cortisol is the primary glucocorticoid that is produced primarily in the
zona fasciculata The ''zona fasciculata'' (sometimes, fascicular or fasciculate zone) constitutes the middle and also the widest zone of the adrenal cortex, sitting directly beneath the ''zona glomerulosa''. Constituent cells are organized into bundles or "fascicl ...
of the adrenal cortex. Corticosterone has only weak
glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every verteb ...
and mineralocorticoid potencies in humans and is important mainly as an intermediate in the steroidogenic pathway from
pregnenolone Pregnenolone (P5), or pregn-5-en-3β-ol-20-one, is an endogenous steroid and precursor/ metabolic intermediate in the biosynthesis of most of the steroid hormones, including the progestogens, androgens, estrogens, glucocorticoids, and mineraloc ...
to aldosterone. Corticosterone is converted to aldosterone by
aldosterone synthase Aldosterone synthase, also called steroid 18-hydroxylase, corticosterone 18-monooxygenase or P450C18, is a steroid hydroxylase cytochrome P450 enzyme involved in the biosynthesis of the mineralocorticoid aldosterone and other steroids. The enzyme ...
, found only in the mitochondria of glomerulosa cells. Glomerulosa cells are found in the Zona glomerulosa, which is the most superficial region of endocrine cells in the adrenal cortex. Corticosterone is the precursor molecule to the mineralocorticoid aldosterone, one of the major homeostatic modulators of sodium and potassium levels in vivo.


Release or generation mechanisms

One example of a release pathway relates to
UV-B Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nm (with a corresponding frequency around 30  PHz) to 400 nm (750  THz), shorter than that of visible light, but longer than X-rays. UV radiation i ...
stimulation on the skins of certain amphibians such as the
Rough-skinned Newt The rough-skinned newt or roughskin newt (''Taricha granulosa'') is a North American newt known for the strong toxin exuded from its skin. Appearance A stocky newt with rounded snout, it ranges from light brown to olive or brownish-black on ...
, '' Taricha granulosa''; this trigger seems to cause the internal generation of corticosterone in that species.


Corticosterone in birds

A sizable amount of research has been done on the effects of corticosterone in birds. A brief survey of this research is below. Corticosterone both inhibits protein synthesis and degrades proteins. Birds with increased levels of corticosterone will have slower feather growth during their molting period and an extended period of poor flight. As a result, many birds have reduced levels of corticosterone when they
moult In biology, moulting (British English), or molting (American English), also known as sloughing, shedding, or in many invertebrates, ecdysis, is the manner in which an animal routinely casts off a part of its body (often, but not always, an outer ...
so as to prevent the degradation of their new feathers. Interestingly, higher levels of corticosterone are also associated with a wider range of exploration, despite beforementioned inhibited feather growth. Corticosterone has further developmental effects on birds. Increased levels of corticosterone in chicks leads to increased begging for food and
aggressiveness Aggression is overt or covert, often harmful, social interaction with the intention of inflicting damage or other harm upon another individual; although it can be channeled into creative and practical outlets for some. It may occur either reacti ...
. In the short term this leads to higher chance of obtaining food, but in the long term, increased corticosterone in early life compromises the birds cognitive functioning ( problem solving, association of visual cue with food, etc.). Parental response to increased begging by chicks is an increased time
foraging Foraging is searching for wild food resources. It affects an animal's fitness because it plays an important role in an animal's ability to survive and reproduce. Foraging theory is a branch of behavioral ecology that studies the foraging behavi ...
for food. This leaves the nest of chicks without protection for increased durations of time. To counter this, during extended periods of food shortage, chicks of some species may suppress corticosterone activity and thus reduce the negative effects elevated corticosterone induces.


Effect on memory

Corticosterone has multiple effects on
memory Memory is the faculty of the mind by which data or information is encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remembered ...
. The main effects are seen through the impact of
stress Stress may refer to: Science and medicine * Stress (biology), an organism's response to a stressor such as an environmental condition * Stress (linguistics), relative emphasis or prominence given to a syllable in a word, or to a word in a phrase ...
on emotional memories as well as
long term memory Long-term memory (LTM) is the stage of the Atkinson–Shiffrin memory model in which informative knowledge is held indefinitely. It is defined in contrast to short-term and working memory, which persist for only about 18 to 30 seconds. Long-te ...
(LTM). With emotional memories, corticosterone is largely associated with
fear Fear is an intensely unpleasant emotion in response to perceiving or recognizing a danger or threat. Fear causes physiological changes that may produce behavioral reactions such as mounting an aggressive response or fleeing the threat. Fear ...
memory recognition. Studies have shown that when fear memories are reactivated or consolidated, levels of corticosterone increased. The increase in corticosterone is linked to anxiety relief. This finding depends on the time at which the administration of corticosterone took place as compared to when the fear conditioning took place; corticosterone can either facilitate or interrupt conditioned fear. Not only does corticosterone have effects on emotional memories but memory recognition and consolidation as well. With respect to recognition and long term memories, corticosterone has variable effects. Studies show that the modification of certain chemical and brain processes that affect corticosterone levels can also impact stress effects on memory. In studies on rats, the fluctuations of corticosterone concentration are shown to prevent stress’ impairment of recognition memory in lower amounts. These lower levels seem to be linked to the rescue of stress-induced attenuation of CA1 long-term potentiation. When researchers looked at stress effects on LTM, they found many outcomes. In multiple studies, the formation of LTM (tested 24 h later) was found to be enhanced by corticosterone in some studies, while the persistence of LTM (tested at least 1 wk later) was only assisted by corticosterone in the late phase of memory consolidation and reconsolidation.S. Moore et al. 2013. Conversion of short-term to long-term memory in the novel object recognition paradigm. Neurobiology of Learning and Memory. 105: 174-185.C. Yang et al. 2013. Stress within a Restricted Time Window Selectively Affects the Persistence of Long-Term Memory. PLoS One. 8(3): e59075. Stress facilitates the consolidation but disrupts the reconsolidation of emotional memory. As mentioned previously, the persistence of LTM is selectively enhanced when stress and corticosterone are administered during the late phase after acquisition, but it is disrupted when stress and corticosterone are administered during the late phase after retrieval of memory. With regards to the persistence of LTM, there is a restricted time window between acquisition and retrieval where persistence is affected. These studies found that while persistence of LTM is selectively affected based on stage of memory, the formation of LTM is left intact after a certain length of time. Up to this point, studies have not agreed as to whether or not these processes are dependent on corticosterone or what even happens based on corticosterone in these processes and how memory is ultimately affected. In the end, corticosterone affects many processes in terms of memory as well as different types of memories themselves.


Additional images

File:Steroidogenesis.svg,
Steroidogenesis A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and ...
File:11-Deoxycorticosterone.svg, Deoxycorticosterone File:Aldosterone-2D-skeletal.svg, Aldosterone


See also

*
11-Deoxycortisol 11-Deoxycortisol, also known as cortodoxone (INN), cortexolone as well as 17α,21-dihydroxyprogesterone or 17α,21-dihydroxypregn-4-ene-3,20-dione, is an endogenous glucocorticoid steroid hormone, and a metabolic intermediate towards cortisol. It ...
* 11-Deoxycorticosterone * Cortisol


References


External links


Corticosterone MS Spectrum
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