CORTISOL METABOLISM AND ITS INHIBITION BY GLYCYRRHETINIC ACID IN THE ISOLATED-PERFUSED HUMAN PLACENTAL LOBULE

We have previously reported the placental metabolism of prednisolone t o prednisone, 20 alpha- and beta-dihydroprednisone and 20 beta-dihydro prednisolone. In this study, the disposition of cortisol was investiga ted in vitro in the dual perfused, isolated human placental lobule aft er the addition of cortisol (1.2 mu mol, n = 3 and 12 mu mol, n = 4) t o the maternal compartment. Analysis of 5 h maternal and fetal perfusa te samples by high performance liquid chromatography-electrospray-tand em mass spectrometry (HPLC-ESI-MS/MS) revealed that cortisol was mainl y metabolized to cortisone, but a significant production of 20 alpha-d ihydrocortisone, 20 beta-dihydrocortisone, 20 alpha-dihydrocortisol an d 20 beta-dihydrocortisol was also detected. Saturability of metabolis m but not transfer was demonstrated. Metabolism was eliminated by co-p erfusion with the potent 11 beta-hydroxysteroid dehydrogenase (11 beta -HSD) enzyme inhibitor 18 beta-glycyrrhetinic acid (GA). The dispositi on of GA was analysed using HPLC-atmospheric pressure chemical ionisat ion-MS/MS (HPLC-APCI-MS/MS). GA was found to transfer from the materna l to the fetal circulations without detectable metabolism during 6 h o f perfusion. (C) 1997 Elsevier Science Ltd.