[11 beta-hydroxysteroid dehydrogenase and steroid receptors].
11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD), as its name implies, is the enzyme responsible for the conversion of cortisol to cortisone, and of corticosterone to 11-dehydrocorticosterone. Ulick et al. reported the detailed investigation of a patient with the syndrome of apparent mineralocorticoid excess (AME), who had the stigmata of florid hyperaldosteronism but low normal or suppressed levels of renin and aldosterone. Such patients show marked abnormalities of cortisol metabolism. From a series of studies, the consensus grew that AME reflects the absence, or very low activity, of 11 beta-HSD in the kidney of affected patients. In addition to providing a framework for understanding the pathogenesis of AME, these studies prompted a re-evaluation of other areas of steroid in the kidney. Glycyrrhetinic acid, the active principle of liquorice and carbenoxolone, exerted its mineralocorticoid action not by a direct effect on mineralocorticoid receptors but by inhibiting renal 11 beta-HSD, thus producing a mild, drug-induced form of AME. Recently Monder et al. reported the cloning and expression of rat and human cDNA encoding corticosteroid 11 beta-dehydrogenase. The physiological role of 11 beta-HSD in conferring aldosterone-selectivity on otherwise non-selective type I receptors has been focused using the genetic method in addition to the biological ones.
Takeda
R
R
Second Department of Internal Medicine, School of Medicine, Kanazawa University, Japan.
Takeda
Y
Y
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000450:Aldosterone / Q000378:metabolism; D002229:Carbenoxolone / Q000494:pharmacology; D006034:Glycyrrhetinic Acid / Q000494:pharmacology; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D007668:Kidney / Q000201:enzymology; D008901:Mineralocorticoids / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism*
D008901:Mineralocorticoids; D011987:Receptors, Steroid; D000450:Aldosterone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D002229:Carbenoxolone; D006034:Glycyrrhetinic Acid