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 interconversion of active glucocorticoids (cortisol, corticosterone) and their inert Il-keto derivatives (cortisone, 11-dehydrocorticosterone). The type-2 isozyme (11 beta-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 11 beta-HSD-2 are responsible for the syndrome of apparent mineralocorticoid excess, in which cortisol illicitly occupies mineralocorticoid receptors, causing hypertension and hypokalaemia. 11 beta-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. 11 beta-HSD-1 is probably an 11 beta-reductase in vivo. Its function is obscure, but may amplify glucocorticoid action during the diurnal nadir, drawing upon the substantial circulating levels of Il-keto steroids. Both isozymes are regulated during ontogeny and by a series of hormonal and other factors. 11 beta-HSD provide an important control of glucocorticoid action at a cellular level, and may represent new targets for therapeutic intervention.