title: Cellular selectivity of aldosterone action: role of 11 beta-hydroxysteroid dehydrogenase.
abstract: Mineralocorticoid receptors in the distal nephron have no intrinsic specificity for mineralocorticoids over glucocorticoids (cortisol in humans; corticosterone in rodents), but are protected from glucocorticoids by the enzyme 11 beta-hydroxysteroid dehydrogenase, which inactivates these steroids to cortisone and 11-dehydrocorticosterone, respectively. Recent work has demonstrated that the enzyme is expressed as multiple tissue-specific isoforms, some of which catalyse the reverse conversion of cortisone to cortisol. These isoforms may allow 11 beta-hydroxysteroid dehydrogenase to modulate access of ligands to glucocorticoid and mineralocorticoid receptors, as well as to amplify and attenuate tissue responses. 11 beta-hydroxysteroid dehydrogenase-mediated protection of mineralocorticoid receptors fails in congenital 11 beta-hydroxysteroid dehydrogenase deficiency and after inhibition of the enzyme by liquorice. In these circumstances, cortisol-dependent mineralocorticoid excess and hypertension ensue. Recent studies suggest that similar deficiencies of 11 beta-dehydrogenase activity may contribute to pathophysiology in common clinical syndromes, illustrating the potential significance of this novel mechanism for development of hypertension.
authors.affiliation: Department of Medicine, Western General Hospital, University of Edinburgh, Scotland, UK.
authors.forename: R
authors.initials: R
authors.lastname: Benediktsson
authors.forename: B R
authors.initials: BR
authors.lastname: Walker
authors.forename: C R
authors.initials: CR
authors.lastname: Edwards
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases; D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology*; D011965:Receptors, Glucocorticoid / Q000378:metabolism
chemical_list: D011965:Receptors, Glucocorticoid; D000450:Aldosterone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases