11 beta-Hydroxysteroid dehydrogenase in renal collecting duct cells.
The purpose of this paper it to briefly review recent work from our laboratory dealing with the form of 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) present in renal aldosterone target cells. It is well established that aldosterone is the physiological mineralocorticoid hormone. The observation that mineralocorticoid receptors have equal affinity for aldosterone and endogenous glucocorticoids, coupled with the fact that circulating levels of glucocorticoids are much higher than those of aldosterone, raises the question of how aldosterone can fulfill its function. To explain this paradox, it was hypothesized that in mineralocorticoid target tissues 11 beta-OHSD rapidly inactivates glucocorticoids (but not aldosterone), thereby decreasing intracellular glucocorticoid levels, so that aldosterone can exert specific regulation via the mineralocorticoid receptor. However, the only form of this enzyme which has been cloned thus far might not be the enzyme which is able to confer aldosterone selectivity on the mineralocorticoid receptor. On the other hand, a new form of 11 beta-OHSD (11 beta-OHSD/CD) that we have discovered in renal collecting duct cells possesses all the properties necessary for protecting the mineralocorticoid receptor: very high affinity for endogenous glucocorticoids, high abundance in target cells, and irreversible dehydrogenase activity. Our hypothesis is that 11 beta-OHSD/CD is the enzyme that ensures aldosterone selectivity in mineralocorticoid target cells, and that is the product of a gene different from the one previously cloned.
Náray-Fejes-Tóth
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A
Department of Physiology, Dartmouth Medical School, Lebanon, NH 03756.
Fejes-Tóth
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G
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D005938:Glucocorticoids / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000201:enzymology*; D007700:Kinetics; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid / Q000502:physiology
D005938:Glucocorticoids; D007527:Isoenzymes; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases