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The genes encoding aldosterone synthase and 11β-hydroxylase are 95% identical and are close together on chromosome 8. In individuals with GRA, there is unequal crossing over so that the 5' regulatory region of the 11-hydroxylase gene is fused to the coding region of the aldosterone synthase. [citation needed]
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 ...
11β-Hydroxylase (CYP11B1) inhibitors such as amphenone B, [20] etomidate, [16] ketoconazole, [16] metyrapone, [16] mitotane, [16] and osilodrostat [25] inhibit the production of the potent corticosteroids cortisol, corticosterone, and aldosterone from the less potent corticosteroids 11-deoxycorticosterone and 11-deoxycortisol and are used in ...
Cholesterol side-chain cleavage enzyme (20,22-desmolase) – steroid synthesis; 17,20-Lyase (17,20-desmolase) – androgen synthesis; Steroid hydroxylases. 11β-Hydroxylase – corticosteroid synthesis; 17α-Hydroxylase – androgen and glucocorticoid synthesis; 18-Hydroxylase (aldosterone synthase) – mineralocorticoid synthesis
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones.Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involved in a wide range of physiological processes, including stress response, immune response, and regulation of inflammation, carbohydrate metabolism ...
Corticosterone is converted to aldosterone by aldosterone synthase, 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 .
Moreover, aldosterone synthase is found within the zona glomerulosa at the outer edge of the adrenal cortex; 11β-hydroxylase is found in the zona glomerulosa and zona fasciculata. Steroidogenesis, showing aldosterone synthesis at upper-right corner. [13] Aldosterone synthase is normally absent in other sections of the adrenal gland. [14]
A mineralocorticoid receptor antagonist (MRA or MCRA) [1] or aldosterone antagonist, is a diuretic drug which antagonizes the action of aldosterone at mineralocorticoid receptors. This group of drugs is often used as adjunctive therapy, in combination with other drugs, for the management of chronic heart failure .