18-Oxocortisol
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18-Oxocortisol
18-Oxocortisol is an endogenous steroid, a metabolite of cortisol. Clinical significance 18-Oxocortisol has been proposed as a biomarker for certain diseases. In humans, 18-oxocortisol has no biological activity on glucocorticoid or mineralocorticoid receptors. In healthy subjects, the biosynthesis of 18-oxocortisol is low. The highest synthesis of 18-oxocortisol was found in certain cases of hypertension like in type 1 familial hyperaldosteronism (glucocorticoid-curable hyperaldosteronism) and type 3 familial hyperaldosteronism, where the adrenal glands are enlarged up to six times their normal size. Increased synthesis is also found in patients with aldosterone-producing adenomas. ACTH stimulation test increases urinary excretion of 18-oxocortisol, and dexamethasone inhibits the excretion. The measurement of 18-oxocortisol using liquid chromatography tandem mass spectrometry has demonstrated its usefulness in distinguishing between unilateral and bilateral forms of primary aldo ...
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18-Hydroxycortisol
18-Hydroxycortisol is an endogenous steroid, a metabolite of cortisol. Clinical significance 18-hydroxycortisol has been proposed as a biomarker for certain diseases. In humans, 18-hydroxycortisol has no biological activity on glucocorticoid or mineralocorticoid receptors. In healthy subjects, the biosynthesis of 18-hydroxycortisol is low. The highest synthesis of 18-hydroxycortisol was found in certain cases of hypertension like in type 1 familial hyperaldosteronism (glucocorticoid-curable hyperaldosteronism) and type 3 familial hyperaldosteronism, where the adrenal glands are enlarged up to six times their normal size. Increased synthesis is also found in patients with aldosterone-producing adenomas. ACTH stimulation test increases urinary excretion of 18-hydroxycortisol, and dexamethasone inhibits the excretion. Biosynthesis In patients with familial hyperaldosteronism type 1, there is a genetic crossover between specific regions of the CYP11B1 and CYP11B2 genes. This cro ...
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Steroid 11β-hydroxylase
Steroid 11β-hydroxylase, also known as steroid 11β-monooxygenase, is a steroid hydroxylase found in the zona glomerulosa and zona fasciculata of the adrenal cortex. Named officially the cytochrome P450 11B1, mitochondrial, it is a protein that in humans is encoded by the ''CYP11B1'' gene. The enzyme is involved in the biosynthesis of Adrenal gland, adrenal corticosteroids by catalyzing the addition of hydroxyl groups during oxidation reactions. Gene The ''CYP11B1'' gene encodes 11β-hydroxylase, a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases that catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. The product of this CYP11B1 gene is the 11β-hydroxylase protein. This protein localizes to the mitochondrial inner membrane and is involved in the conversion of various steroids in the adrenal cortex. Transcript variants encoding different isoforms have been noted for th ...
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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 catalyzes sequential hydroxylations of the steroid angular methyl group at C18 after initial 11β-hydroxylation (the enzyme has steroid 18-hydroxylase activity as well as steroid 11 beta-hydroxylase activity). It is encoded by the gene in humans. Aldosterone synthase is a protein which is only expressed in the zona glomerulosa of the adrenal cortex and is primarily regulated by the renin–angiotensin system. It is the sole enzyme capable of synthesizing aldosterone in humans and plays an important role in electrolyte balance and blood pressure. Genetics Aldosterone synthase is encoded on chromosome 8q22 by the ''CYP11B2'' gene. The gene contains 9 exons and spans roughly 7000 base pairs of DNA. ''CYP11B2'' is closely related with '' ...
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CACNA1D
Calcium channel, voltage-dependent, L type, alpha 1D subunit (also known as Cav1.3) is a protein that in humans is encoded by the ''CACNA1D'' gene. Cav1.3 channels belong to the Cav1 family, which form L-type calcium currents and are sensitive to selective inhibition by dihydropyridines (DHP). Structure and function Voltage-dependent calcium channels (VDCC) are selectively permeable to calcium ions, mediating the movement of these ions in and out of excitable cells. At resting potential, these channels are closed, but when the membrane potential is depolarised these channels open. The influx of calcium ions into the cell can initiate a myriad of calcium-dependent processes including muscle contraction, gene expression, and secretion. Calcium-dependent processes can be halted by lowering intracellular calcium levels, which, for example, can be accomplished by calcium pumps. Voltage-dependent calcium channels are multi-proteins composed of α1, β, α2δ and γ subunits. The m ...
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Pregnanes
Pregnane, also known as 17β-ethylandrostane or as 10β,13β-dimethyl-17β-ethylgonane, is a C21 steroid and, indirectly, a parent of progesterone. It is a parent hydrocarbon for two series of steroids stemming from 5α-pregnane (originally allopregnane) and 5β-pregnane (17β-ethyl etiocholane). It has a gonane core. 5β-Pregnane is the parent of pregnanediones, pregnanolones, and pregnanediols, and is found largely in urine as a metabolic product of 5β-pregnane compounds. Pregnanes Pregnanes are steroid derivatives with carbons present at positions 1 through 21. Most biologically significant pregnane derivatives fall into one of two groups: pregnenes and pregnadienes. Another class is pregnatrienes. Pregnenes Pregnenes have a double bond. Examples include: * Cortisone * Hydrocortisone * Progesterone Pregnadienes Pregnadienes have two double bonds. Examples include: * Cyproterone acetate * Danazol Danazol, sold as Danocrine and other brand names, is a me ...
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6β-Hydroxycortisol
6β-Hydroxycortisol is an endogenous steroid. In humans, it is a metabolite of cortisol produced by cytochrome p450-3A monooxygenases, mainly, 6β-hydroxysteroid dehydrogenase (CYP3A4). 6β-hydroxycortisol is used as a biomarker of 6β-hydroxysteroid dehydrogenase (CYP3A4) activity. Drugs that induce CYP3A4 may accelerate cortisol clearance, by accelerating cortisol conversion to 6β-hydroxycortisol, and vice versa: drugs that inhibit CYP3A4 can slow down cortisol clearance, as they reduce the conversion of cortisol to 6β-hydroxycortisol. Biological role Although the exact role of 6β-hydroxycortisol in the human body is not fully understood, it is believed to play an important role in the metabolism and clearance of cortisol. 6β-hydroxycortisol is a metabolite of cortisol: the enzyme 6β-hydroxysteroid dehydrogenase (CYP3A4) catalyzes the formation of 6β-hydroxycortisol from cortisol in the liver and other tissues; the resulting 6β-hydroxycortisol is excreted in urine. 6β-hyd ...
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18-Hydroxycorticosterone
18-Hydroxycorticosterone is an endogenous steroid. It is a derivative of corticosterone. Function 18-Hydroxycorticosterone serves as an intermediate in the synthesis of aldosterone by the enzyme aldosterone synthase in the zona glomerulosa. It is also an intermediate in the biosynthesis of corticosterone. It spontaneously and reversibly converts to various less polar forms and derivatives, some of which serve as precursors to aldosterone or corticosterone. Specifically, 21-hydroxy-11,18-oxido-4-pregnene-3,20-dione (18-DAL) is hydroxylated to aldosterone in the presence of malate and NADP+ at pH 4.8, indicating that 18-DAL acts as a metabolic intermediate between 18-hydroxycorticosterone and aldosterone. Corticosterone is a mediate precursor in this biosynthesis pathway, with 18-hydroxycorticosterone serving as an intermediate between corticosterone and aldosterone. See also * 18-Hydroxycortisol * Aldosterone synthase Aldosterone synthase, also called steroid 18-hydroxylase, c ...
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Cortisol
Cortisol is a steroid hormone in the glucocorticoid class of hormones and a stress hormone. When used as medication, it is known as hydrocortisone. Cortisol is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal cortex in an adrenal gland. In other tissues, it is produced in lower quantities. By a Circadian rhythm, diurnal cycle, cortisol is released and increases in response to Stress (biology), stress and a low Blood sugar, blood-glucose concentration. It functions to increase blood sugar through gluconeogenesis, suppress the immune system, and aid in the metabolism of calories. It also decreases bone formation. These stated functions are carried out by cortisol binding to glucocorticoid or mineralocorticoid receptors inside a cell, which then bind to DNA to affect gene expression. Health effects Metabolic response Metabolism of glucose Cortisol plays a crucial role in regulating glucose metabolism and promotes gluconeogenesis (glucose synthes ...
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Biosynthesis
Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme-Catalysis, catalyzed processes where chemical substances absorbed as nutrients (or previously converted through biosynthesis) serve as enzyme substrate (chemistry), substrates, with conversion by the living organism either into simpler or more complex Product (chemistry), products. Examples of biosynthetic pathways include those for the production of amino acids, lipid membrane components, and nucleotides, but also for the production of all classes of biological macromolecules, and of acetyl-coenzyme A, adenosine triphosphate, nicotinamide adenine dinucleotide and other key intermediate and transactional molecules needed for metabolism. Thus, in biosynthesis, any of an array of Chemical compound, compounds, from simple to complex, are converted into other compounds, and so it includes both the catabolism and anabolism (building up and breaking down) of comple ...
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Adrenocorticotropic Hormone
Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological stress (along with its precursor corticotropin-releasing hormone from the hypothalamus). Its principal effects are increased production and release of cortisol and androgens by the zona fasiculata and zona reticularis, respectively. ACTH is also related to the circadian rhythm in many organisms. Deficiency of ACTH is an indicator of secondary adrenal insufficiency (suppressed production of ACTH due to an impairment of the pituitary gland or hypothalamus, cf. hypopituitarism) or tertiary adrenal insufficiency (disease of the hypothalamus, with a decrease in the release of corticotropin releasing hormone (CRH)). Conversely, chronically e ...
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