Cortisol metabolism and its inhibition by glycyrrhetinic acid in the isolated perfused human placental lobule

  • J Steroid Biochem Mol Biol. 1997 Jul;62(4):337-43. doi: 10.1016/s0960-0760(97)00039-3.
H M Dodds  1 ,  P J Taylor ,  L P Johnson ,  R H Mortimer ,  S M Pond ,  G R Cannell
Affiliations
  • 1. University of Queensland, Department of Medicine, Princess Alexandra Hospital, Brisbane, Australia. [email protected]
PMID: 9408088 DOI: 10.1016/s0960-0760(97)00039-3
Abstract

We have previously reported the placental metabolism of prednisolone to prednisone, 20alpha- and beta-dihydroprednisone and 20beta-dihydroprednisolone. In this study, the disposition of cortisol was investigated in vitro in the dual perfused, isolated human placental lobule after the addition of cortisol (1.2 micromol, n = 3 and 12 micromol, n = 4) to the maternal compartment. Analysis of 5 h maternal and fetal perfusate samples by high performance liquid chromatography-electrospray-tandem mass spectrometry (HPLC-ESI-MS/MS) revealed that cortisol was mainly metabolized to cortisone, but a significant production of 20alpha-dihydrocortisone, 20beta-dihydrocortisone, 20alpha-dihydrocortisol and 20beta-dihydrocortisol was also detected. Saturability of metabolism but not transfer was demonstrated. Metabolism was eliminated by co-perfusion with the potent 11beta-hydroxysteroid dehydrogenase (11beta-HSD) enzyme inhibitor 18beta-glycyrrhetinic acid (GA). The disposition of GA was analysed using HPLC-atmospheric pressure chemical ionisation-MS/MS (HPLC-APCI-MS/MS). GA was found to transfer from the maternal to the fetal circulations without detectable metabolism during 6 h of perfusion.

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