THE 11-BETA-HYDROXYSTEROID DEHYDROGENASE SYSTEM, A DETERMINANT OF GLUCOCORTICOID AND MINERALOCORTICOID ACTION - MEDICAL AND PHYSIOLOGICAL-ASPECTS OF THE 11-BETA-HYDROXYSTEROID DEHYDROGENASE SYSTEM

11 beta-Hydroxysteroid dehydrogenases (11 beta-HSD) catalyse the inter conversion of active glucocorticoids (cortisol, corticosterone) and th eir inert Il-keto derivatives (cortisone, 11-dehydrocorticosterone). T he type-2 isozyme (11 beta-HSD-2) is a high-affinity dehydrogenase tha t catalyses the rapid inactivation of glucocorticoids, thus ensuring s elective access of aldosterone to otherwise non-selective mineralocort icoid receptors in the distal nephron. Mutations of the gene encoding 11 beta-HSD-2 are responsible for the syndrome of apparent mineralocor ticoid excess, in which cortisol illicitly occupies mineralocorticoid receptors, causing hypertension and hypokalaemia. 11 beta-HSD-2 is als o highly expressed in the placenta and mid-gestation fetus, where it m ay protect developing tissues from the often deleterious actions of gl ucocorticoids upon fetal growth and organ maturation. 11 beta-HSD-1 is probably an 11 beta-reductase in vivo. Its function is obscure, but m ay amplify glucocorticoid action during the diurnal nadir, drawing upo n the substantial circulating levels of Il-keto steroids. Both isozyme s are regulated during ontogeny and by a series of hormonal and other factors. 11 beta-HSD provide an important control of glucocorticoid ac tion at a cellular level, and may represent new targets for therapeuti c intervention.