PLACENTAL 11-BETA-HYDROXYSTEROID DEHYDROGENASE - A KEY REGULATOR OF FETAL GLUCOCORTICOID EXPOSURE

OBJECTIVE Placental 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) , which converts active cortisol to inactive cortisone, has been propo sed to be the mechanism guarding the fetus from the growth retarding e ffects of maternal glucocorticoids; however, other placental enzymes h ave also been implicated. Placental 11 beta-HSD is unstable in vitro, and enzyme activity thus detected may not be relevant to the proposed barrier role. We have therefore examined placental glucocorticoid meta bolism in dually perfused freshly isolated intact human placentas. DES IGN Placentas were obtained from randomly selected normal term deliver ies. The maternal circuit was perfused with physiological concentratio n of cortisol, the fetal effluent collected and steroid metabolites se parated and quantified using silica columns (Sep-pak Plus) and HPLC. R ESULTS Most of the maternally administered cortisol was metabolized to cortisone, and no conversion of cortisone to cortisol was detected. C ortisone was the only product of cortisol metabolism. Inhibition of 11 beta-HSD with glycyrrhetinic acid allowed cortisol to gain direct acc ess to the fetal circulation. CONCLUSION We conclude that human placen tal 11 beta-HSD plays a crucial role in controlling glucocorticoid acc ess to the fetus. Other enzymes are not significant contributors at ph ysiologically relevant cortisol concentrations.