Maternal drug abuse and human term placental xenobiotic and steroid metabolizing enzymes in vitro

We evaluated the impact of maternal drug abuse at term on human placental c ytochrome P450 (CYP)-mediated (Phase I) xenobiotic and steroid-metabolizing activities [aromatase, 7-ethoxyresorufin O-deethylase (EROD), 7-ethoxycoum arin O-deethylase (ECOD), pyrene 1-hydroxylase (P1OH), and testosterone hyd roxylase], and androstenedione-forming isomerase, NADPH quinone oxidoreduct ase (Phase II), UDP-glucuronosyltransferase (UGT), and glutathione S-transf erase (GST) activities in vitro. Overall, the formation of androstenedione, P1OH, and testosterone hydroxylase was statistically significant between c ontrol and drug-abusing subjects; we observed no significant differences in any other of the phase I and II activities. In placentas from drug-abusing mothers, we found significant correlations between ECOD and P1OH activitie s (p < 0.001), but not between ECOD and aromatase or P1OH and EROD activiti es; we also found significant correlations between blood cotinine and UGT a ctivities (p < 0.01). In contrast, in controls (mothers who did not abuse d rugs but did smoke cigarettes), the P1OH activity correlated with ECOD, ERO D (p < 0.001), and testosterone hydroxylase (p < 0.001) activities. Out res ults (wider variation in ECOD activity among tissue from drug-abusing mothe rs and the significant correlation between P1OH and ECOD activities, but no t with aromatase or EROD activities) indicate that maternal drug abuse resu lts in an additive effect in enhancing placental xenobiotic metabolizing en zymes when the mother also smokes cigarettes; this may be due to enhancing a "silent" CYP form, or a new placental CYP form may be activated. The chan ge in the steroid metabolism profile in vitro suggests that maternal drug a buse may alter normal hormonal homeostasis during pregnancy.