Medical and physiological aspects of the 11beta-hydroxysteroid dehydrogenase system.
11Beta-hydroxysteroid dehydrogenases (11beta-HSD) catalyse the interconversion of active glucocorticoids (cortisol, corticosterone) and their inert 11-keto derivatives (cortisone, 11-dehydrocorticosterone). The type-2 isozyme (11beta-HSD-2) is a high-affinity dehydrogenase that catalyses the rapid inactivation of glucocorticoids, thus ensuring selective access of aldosterone to otherwise non-selective mineralocorticoid receptors in the distal nephron. Mutations of the gene encoding 11beta-HSD-2 are responsible for the syndrome of apparent mineralocorticoid excess, in which cortisol illicitly occupies mineralocorticoid receptors, causing hypertension and hypokalaemia. 11Beta-HSD-2 is also highly expressed in the placenta and mid-gestation fetus, where it may protect developing tissues from the often deleterious actions of glucocorticoids upon fetal growth and organ maturation. 11Beta-HSD-1 is probably an 11beta-reductase in vivo. Its function is obscure, but may amplify glucocorticoid action during the diurnal nadir, drawing upon the substantial circulating levels of 11-keto steroids. Both isozymes are regulated during ontogeny and by a series of hormonal and other factors. 11Beta-HSD provide an important control of glucocorticoid action at a cellular level, and may represent new targets for therapeutic intervention.
Seckl
J R
JR
Molecular Endocrinology Unit, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, UK. j.seckl@ed.ac.uk
Chapman
K E
KE
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D005260:Female; D005333:Fetus / Q000502:physiology; D005938:Glucocorticoids / Q000378:metabolism; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D008661:Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics; D008901:Mineralocorticoids / Q000378:metabolism; D010920:Placenta / Q000502:physiology; D011247:Pregnancy; D013379:Substrate Specificity
D005938:Glucocorticoids; D007527:Isoenzymes; D008901:Mineralocorticoids; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases