11 beta-Hydroxysteroid dehydrogenase.
In mammalian tissues, at least two isozymes of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) catalyze the interconversion of hormonally active C11-hydroxylated corticosteroids (cortisol, corticosterone) and their inactive C11-keto metabolites (cortisone, 11-dehydrocorticosterone). The type 1 and type 2 11 beta-HSD isozymes share only 14% homology and are separate gene products with different physiological roles, regulation, and tissue distribution. 11 beta-HSD2 is a high affinity NAD-dependent dehydrogenase that protects the mineralocorticoid receptor from glucocorticoid excess; mutations in the HSD11B2 gene explain an inherited form of hypertension, the syndrome of apparent mineralocorticoid excess in which cortisol acts as a potent mineralocorticoid. By contrast, 11 beta-HSD1 acts predominantly as a reductase in vivo, facilitating glucocorticoid hormone action in key target tissues such as liver and adipose tissue. Over the 10 years, 11 beta-HSD has progressed from an enzyme merely involved in the peripheral metabolism of cortisol to a crucial pre-receptor signaling pathway in the analysis of corticosteroid hormone action. This review details the enzymology, molecular biology, distribution, regulation, and function of the 11 beta-HSD isozymes and highlights the clinical consequences of altered enzyme expression.
Stewart
P M
PM
Department of Medicine, University of Birmingham, Queen Elizabeth Hospital, United Kingdom.
Krozowski
Z S
ZS
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000305:Adrenal Cortex Hormones / Q000378:metabolism / Q000502:physiology; D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000502:physiology; D007527:Isoenzymes / Q000235:genetics; D009154:Mutation; D011987:Receptors, Steroid / Q000502:physiology; D014018:Tissue Distribution
D000305:Adrenal Cortex Hormones; D007527:Isoenzymes; D011987:Receptors, Steroid; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases