INTRAHEPATIC CHOLESTASIS OF PREGNANCY IMPAIRS THE ACTIVITIES OF HUMANPLACENTAL XENOBIOTIC AND STEROID METABOLIZING ENZYMES IN-VITRO

Human placental xenobiotic metabolizing and aromatase activities were measured in placentae at term obtained from pregnancies diagnosed as i ntrahepatic cholestasis (IC). Compared with controls, several cytochro me P450-dependent (CYP) mono-oxygenases were significantly decreased i n IC placentae: 7-ethoxycoumarin O-deethylase by 75 per cent, 7-ethoxy resorufin O-deethylase by 95 per cent, aromatase activity by 37 per ce nt and androstenedione formation, using testosterone as a substrate, b y 20 per cent. These results demonstrate that maternal intrahepatic ch olestasis effectively decreases CYP dependent metabolism in human plac enta in vitro which may pose a potential risk to the wellbeing of the fetus. Because aromatase activity in IC placentae is significantly low er as compared with healthy controls, safety of the drug therapies whi ch further inhibit aromatase activity are questioned. (C) 1997 W. B. S aunders Company Ltd.