Mechanism of aldosterone action in the distal nephron . Aldosterone, the predominant human mineralocorticoid hormone, enters distal nephron cells through the plasma membrane and interacts with its receptor (the mineralocorticoid receptor [MR], or Type I receptor). Interaction between aldosterone and this receptor initiates induction of new proteins that, by way of mechanisms that remain unclear, increase the number of sodium channels (ENaC) and sodium-potassium adenosine triphosphatase (Na-K ATPase) pumps at the cell surface. This increases transepithelial Na (and potassium) transport. Cortisol, the predominant human glucocorticoid hormone, also enters cells through the plasma membrane and interacts with its receptor (the glucocorticoid receptor [GR]). Cortisol, however, also interacts with mineralocorticoid receptors; the affinity of cortisol and aldos-terone for mineralocorticoid receptors is approximately equal. In distal nephron cells, this interaction also stimulates electrogenic Na transport . Cortisol normally circulates at concentrations 100 to 1000 times higher than the circulating concentration of aldosterone. In aldosterone-responsive tissues, such as the distal nephron, expression of the enzyme 11|3-hydroxysteroid dehydrogenase (11|3-HSD) permits rapid metabolism of cortisol so that only aldosterone can stimulate Na transport in these cells. An inherited deficiency of the enzyme 11^-HSD (the syndrome of apparent mineralocorticoid excess, AME), or inhibition of the enzyme by ingestion of licorice, leads to hypertension owing to chronic stimulation of distal Na transport by endogenous glucocorticoids .
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