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Mineralocorticoids is a class of steroids characterised by their similarity to aldosterone and their influence on salt and water metabolism.
Physiology The primary endogenous mineralocorticoid is aldosterone, although a number of other endogenous hormones (including progesterone)and deoxycorticosterone have mineralocorticoid function. Aldosterone acts on the kidneys to provide active reabsorption of sodium and an associated passive reabsorption of water, as well as, the active secretion of potassium in the principle cells of the cortical collecting tubule and active secretion of protons via proton ATPases in the lumenal membrane of the intercalated cells of the collecting tubule. This in turn results in an increase of blood pressure and blood volume. Aldosterone is produced in the cortex of the adrenal gland and its secretion is mediated by adrenocorticotrophic hormone (ACTH). Mode of Action Mineralocorticoids bind to the cytosolic mineralocorticoid receptor. This type of receptor gets activated upon ligand binding. After a hormone binds to the corresponding receptor, the newly formed receptor-ligand complex translocates itself into the cell nucleus, where it binds to many hormone response elements (HRE) in the promoter region of the target genes in the DNA. The opposite mechanism is called transrepression. The activated hormone receptor interacts with specific transcription factors and prevents the transcription of targeted genes. Aldosterone and cortisol have similar affinity for the mineralocorticoid receptor however, glucocorticoids circulate at roughly 100 times the level of mineralocorticoids. An enzyme exists in mineralocorticoid target tissues to prevent overstimulation by glucocorticoids. This enzyme, 11-beta hydroxysteroid dehydrogenase type II(Protein:HSD11B2), catalyzes the deactivation of glucocorticoids to 11-dehydro metabolites. Licorice is known to be an inhibitor of this enzyme and chronic consumption can result in a condition known as pseudohyperaldosteronism. Pathophysiology Hyperaldosteronism (the syndrome caused by elevated aldosterone) generally results from adrenal neoplasms. The two main resulting problems: Underproduction, or hypoaldosteronism, leads to the salt-wasting state associated with Addison's disease, although classical congenital adrenal hyperplasia and other disease states may also cause this situation. Pharmacology An example of synthetic mineralocorticoids is fludrocortisone (Florinef®). An important mineralocorticoid inhibitor is spironolactone. | ||||||||
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