title: Molecular biology of mineralocorticoid metabolism.
abstract: Mineralocorticoids are adrenal steroid hormones that regulate the retention of sodium by the kidney and, hence, are crucial in the regulation of sodium balance, intravascular volume, and blood pressure. The molecular biology of mineralocorticoid biosynthesis and action has only recently been elucidated. The genes encoding the various enzymes that convert cholesterol to mineralocorticoids have now been cloned. This has revealed the molecular basis of several inherited forms of mineralocorticoid excess, which cause hypertension, and several forms of mineralocorticoid deficiency, which cause salt loss. The cloning of the mineralocorticoid receptor revealed a paradox. Both the mineralocorticoid and the glucocorticoid receptor are activated equally by cortisol, even though cortisol has very modest mineralocorticoid activity. This is explained by the cloning of two genes for the enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta HSD). Type-II 11 beta HSD, found primarily in the kidney, irreversibly converts cortisol to cortisone, which does not activate the mineralocorticoid receptor. Type-II 11 beta HSD thus defends the mineralocorticoid receptor from being activated by the very high concentrations of cortisol in the blood. Recent studies in genetically hypertensive rats suggest that other enzymes or factors that regulate salt balance may remain undiscovered. Thus the study of mineralocorticoid biosynthesis and action remains one of the most promising approaches to understanding hypertension.
authors.affiliation: Departamento de Endocrinologia, Universidad Católica de Chile, Santiago, Chile.
authors.forename: C E
authors.initials: CE
authors.lastname: Fardella
authors.forename: W L
authors.initials: WL
authors.lastname: Miller
mesh_terms: D000818:Animals; D006801:Humans; D006973:Hypertension / Q000235:genetics; D008901:Mineralocorticoids / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D018161:Receptors, Mineralocorticoid / Q000737:chemistry / Q000502:physiology; D019282:Wasting Syndrome / Q000235:genetics
chemical_list: D008901:Mineralocorticoids; D018161:Receptors, Mineralocorticoid