Intrahepatic cholestasis of pregnancy impairs the activities of human placental 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 intrahepatic cholestasis (IC). Compared with controls, several cytochrome P450-dependent (CYP) mono-oxygenases were significantly decreased in IC placentae: 7-ethoxycoumarin O-deethylase by 75 per cent, 7-ethoxyresorufin O-deethylase by 95 per cent, aromatase activity by 37 per cent and androstenedione formation, using testosterone as a substrate, by 20 per cent. These results demonstrate that maternal intrahepatic cholestasis effectively decreases CYP dependent metabolism in human placenta in vitro which may pose a potential risk to the wellbeing of the fetus. Because aromatase activity in IC placentae is significantly lower as compared with healthy controls, safety of the drug therapies which further inhibit aromatase activity are questioned.
Pasanen
M
M
Department of Pharmacology and Toxicology, University of Oulu, Finland.
Helin-Martikainen
H L
HL
Pelkonen
O
O
Kirkinen
P
P
D000328:Adult; D000735:Androstenedione / Q000378:metabolism; D002624:Chemistry, Clinical; D002780:Cholestasis, Intrahepatic / Q000201:enzymology* / Q000503:physiopathology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008861:Microsomes; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000201:enzymology* / Q000503:physiopathology; D011263:Pregnancy Trimester, Third
D000735:Androstenedione; D003577:Cytochrome P-450 Enzyme System