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DHEA-S
Dehydroepiandrosterone sulfate, abbreviated as DHEA sulfate or DHEA-S, also known as androstenolone sulfate, is an endogenous androstane steroid that is produced by the adrenal cortex. It is the 3β-sulfate ester and a metabolite of dehydroepiandrosterone (DHEA) and circulates in far greater relative concentrations than DHEA. The steroid is hormonally inert and is instead an important neurosteroid and neurotrophin. Biological activity Neurosteroid activity Similarly to other conjugated steroids, DHEA-S is devoid of hormonal activity, lacking affinity for the steroid hormone receptors. However, DHEA-S retains activity as a neurosteroid and neurotrophin. It has been found to act as a positive allosteric modulator of the NMDA receptor (50 nM–1 μM), negative allosteric modulator of the GABAA and glycine receptors, and weak agonist of the sigma-1 receptor (Kd > 50 μM). In addition, DHEA-S has been found to directly bind to and activate the TrkA and p7 ...
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Dehydroepiandrosterone
Dehydroepiandrosterone (DHEA), also known as androstenolone, is an endogenous steroid hormone precursor. It is one of the most abundant circulating steroids in humans. DHEA is produced in the adrenal glands, the gonads, and the brain. It functions as a metabolic intermediate in the biosynthesis of the androgen and estrogen sex steroids both in the gonads and in various other tissues. However, DHEA also has a variety of potential biological effects in its own right, binding to an array of nuclear and cell surface receptors, and acting as a neurosteroid and modulator of neurotrophic factor receptors. In the United States, DHEA is sold as an over-the-counter supplement, and medication called prasterone. Biological function As an androgen DHEA and other adrenal androgens such as androstenedione, although relatively weak androgens, are responsible for the androgenic effects of adrenarche, such as early pubic and axillary hair growth, adult-type body odor, increased oiliness of ...
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Androgen
An androgen (from Greek ''andr-'', the stem of the word meaning "man") is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This includes the embryological development of the primary male sex organs, and the development of male secondary sex characteristics at puberty. Androgens are synthesized in the testes, the ovaries, and the adrenal glands. Androgens increase in both males and females during puberty. The major androgen in males is testosterone. Dihydrotestosterone (DHT) and androstenedione are of equal importance in male development. DHT ''in utero'' causes differentiation of the penis, scrotum and prostate. In adulthood, DHT contributes to balding, prostate growth, and sebaceous gland activity. Although androgens are commonly thought of only as male sex hormones, females also have them, but at lower levels: they function in libido and sexual arousal. Also, an ...
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Neurosteroid
Neurosteroids, also known as neuroactive steroids, are endogenous or exogenous steroids that rapidly alter neuronal excitability through interaction with ligand-gated ion channels and other cell surface receptors. The term ''neurosteroid'' was coined by the French physiologist Étienne-Émile Baulieu and refers to steroids synthesized in the brain. The term, ''neuroactive steroid'' refers to steroids that can be synthesized in the brain, or are synthesized by an endocrine gland, that then reach the brain through the bloodstream and have effects on brain function. The term neuroactive steroids was first coined in 1992 by Steven Paul and Robert Purdy. In addition to their actions on neuronal membrane receptors, some of these steroids may also exert effects on gene expression via nuclear steroid hormone receptors. Neurosteroids have a wide range of potential clinical applications from sedation to treatment of epilepsy and traumatic brain injury. Ganaxolone, a synthetic analog of the end ...
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Sigma-1 Receptor
The sigma-1 receptor (σ1R), one of two sigma receptor subtypes, is a chaperone protein at the endoplasmic reticulum (ER) that modulates calcium signaling through the IP3 receptor. In humans, the σ1 receptor is encoded by the ''SIGMAR1'' gene. The σ1 receptor is a transmembrane protein expressed in many different tissue types. It is particularly concentrated in certain regions of the central nervous system. It has been implicated in several phenomena, including cardiovascular function, schizophrenia, clinical depression, the effects of cocaine abuse, and cancer. Much is known about the binding affinity of hundreds of synthetic compounds to the σ1 receptor. An endogenous ligand for the σ1 receptor has yet to be conclusively identified, but tryptaminergic trace amines and neuroactive steroids have been found to activate the receptor. Especially progesterone, but also testosterone, pregnenolone sulfate, and dehydroepiandrosterone sulfate (DHEA-S) bind to the σ1 receptor. C ...
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Neurotrophin
Neurotrophins are a family of proteins that induce the survival, development, and function of neurons. They belong to a class of growth factors, secreted proteins that can signal particular cells to survive, differentiate, or grow. Growth factors such as neurotrophins that promote the survival of neurons are known as neurotrophic factors. Neurotrophic factors are secreted by target tissue and act by preventing the associated neuron from initiating programmed cell death – allowing the neurons to survive. Neurotrophins also induce differentiation of progenitor cells, to ''form'' neurons. Although the vast majority of neurons in the mammalian brain are formed prenatally, parts of the adult brain (for example, the hippocampus) retain the ability to grow new neurons from neural stem cells, a process known as neurogenesis. Neurotrophins are chemicals that help to stimulate and control neurogenesis. Terminology According to the United States National Library of Medicine's medical sub ...
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NMDA Receptor
The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA receptor, AMPA and kainate receptors. Depending on its subunit composition, its Ligand (biochemistry), ligands are glutamate and glycine (or D-Serine, D-serine). However, the binding of the ligands is typically not sufficient to open the channel as it may be blocked by Magnesium, Mg2+ ions which are only removed when the neuron is sufficiently depolarized. Thus, the channel acts as a “coincidence detector” and only once both of these conditions are met, the channel opens and it allows cation, positively charged ions (cations) to flow through the cell membrane. The NMDA receptor is thought to be very important for controlling synaptic plasticity and mediating learning and memory functions. The NMDA receptor is ionotropic, meaning it is a pr ...
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Adrenal Cortex
The adrenal cortex is the outer region and also the largest part of an adrenal gland. It is divided into three separate zones: zona glomerulosa, zona fasciculata and zona reticularis. Each zone is responsible for producing specific hormones. It is also a secondary site of androgen synthesis. – "Adrenal Gland" Layers The adrenal cortex comprises three main zones, or layers that are regulated by distinct hormones as noted below. This ''anatomic zonation'' can be appreciated at the microscopic level, where each zone can be recognized and distinguished from one another based on structural and anatomic characteristics. ;Zona glomerulosa :The outermost layer, the zona glomerulosa is the main site for the production of aldosterone, a mineralocorticoid. The synthesis and secretion of aldosterone are mainly regulated by the renin–angiotensin–aldosterone system. The zona glomerulosa cells express a specific enzyme aldosterone synthase (also known as CYP11B2). Aldosterone is largel ...
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Estrogen
Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal activity: estrone (E1), estradiol (E2), and estriol (E3). Estradiol, an estrane, is the most potent and prevalent. Another estrogen called estetrol (E4) is produced only during pregnancy. Estrogens are synthesized in all vertebrates and some insects. Their presence in both vertebrates and insects suggests that estrogenic sex hormones have an ancient evolutionary history. Quantitatively, estrogens circulate at lower levels than androgens in both men and women. While estrogen levels are significantly lower in males than in females, estrogens nevertheless have important physiological roles in males. Like all steroid hormones, estrogens readily diffuse across the cell membrane. Once inside the cell, they bind to and activate estrogen receptors (E ...
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Testosterone
Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testes and prostate, as well as promoting secondary sexual characteristics such as increased muscle and bone mass, and the growth of androgenic hair, body hair. In addition, testosterone in both sexes is involved in health and well-being, including moods, behaviour, and in the prevention of osteoporosis. Insufficient levels of testosterone in men may lead to abnormalities including frailty and bone loss. Testosterone is a steroid from the androstane class containing a ketone and a hydroxyl group at positions three and seventeen respectively. It is Biosynthesis, biosynthesized in several steps from cholesterol and is converted in the liver to inactive metabolites. It exerts its action through binding to and activation of the androgen receptor. In humans and most other vertebrates, testost ...
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Glycine Receptor
The glycine receptor (abbreviated as GlyR or GLR) is the receptor of the amino acid neurotransmitter glycine. GlyR is an ionotropic receptor that produces its effects through chloride current. It is one of the most widely distributed inhibitory receptors in the central nervous system and has important roles in a variety of physiological processes, especially in mediating inhibitory neurotransmission in the spinal cord and brainstem. The receptor can be activated by a range of simple amino acids including glycine, β-alanine and taurine, and can be selectively blocked by the high-affinity competitive antagonist strychnine. Caffeine is a competitive antagonist of GlyR. Gephyrin has been shown to be necessary for GlyR clustering at inhibitory synapses. GlyR is known to colocalize with the GABAA receptor on some hippocampal neurons. Nevertheless, some exceptions can occur in the central nervous system where the GlyR α1 subunit and gephyrin, its anchoring protein, are not foun ...
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Dihydrotestosterone
Dihydrotestosterone (DHT, 5α-dihydrotestosterone, 5α-DHT, androstanolone or stanolone) is an endogenous androgen sex steroid and hormone. The enzyme 5α-reductase catalyzes the formation of DHT from testosterone in certain tissues including the prostate gland, seminal vesicles, epididymides, skin, hair follicles, liver, and brain. This enzyme mediates reduction of the C4-5 double bond of testosterone. Relative to testosterone, DHT is considerably more potent as an agonist of the androgen receptor (AR). In addition to its role as a natural hormone, DHT has been used as a medication, for instance in the treatment of low testosterone levels in men; for information on DHT as a medication, see the androstanolone article. Biological function DHT is biologically important for sexual differentiation of the male genitalia during embryogenesis, maturation of the penis and scrotum at puberty, growth of facial, body, and pubic hair, and development and maintenance of the pro ...
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Brain-derived Neurotrophic Factor
Brain-derived neurotrophic factor (BDNF), or abrineurin, is a protein found in the and the periphery. that, in humans, is encoded by the ''BDNF'' gene. BDNF is a member of the neurotrophin family of growth factors, which are related to the canonical nerve growth factor (NGF), a family which also includes NT-3 and NT-4/NT-5. Neurotrophic factors are found in the brain and the periphery. BDNF was first isolated from a pig brain in 1982 by Yves-Alain Barde and Hans Thoenen. BDNF activates the TrkB tyrosine kinase receptor. Function BDNF acts on certain neurons of the central nervous system and the peripheral nervous system expressing TrkB, helping to support survival of existing neurons, and encouraging growth and differentiation of new neurons and synapses. In the brain it is active in the hippocampus, cortex, and basal forebrain—areas vital to learning, memory, and higher thinking. BDNF is also expressed in the retina, kidneys, prostate, motor neurons, and skeletal musc ...
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