The 11beta-hydroxysteroid dehydrogenases: functions and physiological effects.

The 11beta-hydroxysteroid dehydrogenase enzymes (11beta-HSD) interconvert cortisol and cortisone in man, and corticosterone and 11-dehydrocorticosterone in rodents. Two distantly related congeners have been isolated and conserved domains identified by multiple alignment and hydrophobic cluster analysis. 11Beta-HSD1 in the liver acts mainly as an oxoreductase maintaining circulating glucocorticoid levels. Gene deletion studies suggest it plays an important role in providing elevated local concentrations of hormone. In contrast, 11beta-HSD2 inactivates glucocorticoids and is pivotal in the distal tubule where it protects the mineralocorticoid receptor from occupation, thus endowing specificity on a non-selective receptor. Mutations in 11beta-HSD2 result in sodium retention and severe hypertension, account for the syndrome of apparent mineralocorticoid excess and may be responsible for other forms of hypertension. 11Beta-HSD2 is also present in the placenta where it protects the fetus from high circulating levels of maternal glucocorticoids. Attenuated placental 11beta-HSD2 activity has recently been shown to be associated with intrauterine growth retardation. 11Beta-HSD2 may also play important roles in pulmonary physiology and breast cancer. This review focuses on recent developments.