Dual function of 11 beta-hydroxysteroid dehydrogenase in placenta: Modulating placental glucocorticoid passage and local steroid action

Target cell metabolism of glucocorticoids is now recognized as an important modulator of ligand access to the glucocorticoid receptor (GR). This metab olism occurs via two distinct 11 beta-hydroxysteroid dehydrogenase (11 beta -HSD) enzymes (types 1 and 2) that catalyze interconversion of active gluco corticoids (cortisol and corticosterone) and their inactive 11-keto product s (cortisone and 11-dehydrocorticosterone, respectively). The focus of this review is on the biology of the 11 beta-HSD enzymes in the placenta, where they also regulate passage of maternal glucocorticoids to the fetus. The p resence of this metabolic barrier at the maternal-fetal interface is potent ially crucial to fetal growth and development, since maternal glucocorticoi d levels are elevated in pregnancy and since excess glucocorticoid exposure in fetal life has detrimental effects on prenatal growth and increases sus ceptibility to disease in subsequent adult life. In primates, transplacenta l glucocorticoid passage also appears to play an important role in the indu ction of an autonomous fetal hypothalamic-pituitary-adrenal axis near term. Placental 11 beta-HSD is also likely to modulate glucocorticoid actions wi thin the placenta, per se, by regulating their access to placental GR. More over, because some progesterone effects are exerted via the GR, placental 1 1 beta-HSD may regulate progesterone-glucocorticoid competition for access to this receptor and thereby affect the biological actions of both steroids in the placenta.