Mono-oxygenase induction in the human placenta. Interrelationships among position-specific hydroxylations of 17...

An investigation of the specific hydroxylations of aromatic ring carbon atoms 2 and 4 of 17 beta-estradiol (E2) in microsomal fractions of human placental tissues revealed that rates of 4-hydroxylation were elevated 3- to 5-fold in placentas of cigarette smokers. Minor increases in hydroxylation at carbon atom 2 were statistically insignificant. Correlation analyses and studies with inhibitors and activators also strongly indicated that 2-hydroxylase and 4-hydroxylase activities were under separate regulatory control. Attempts to determine possible correlations between placental E2 4-hydroxylase and aryl hydrocarbon (benzo[a]pyrene, BaP) hydroxylase (AHH) activities revealed an unusual threshold-type relationship. With AHH activities of 0-40 pmol/mg/15 min, no-statistically significant correlation existed. With AHH activities above 50 pmol/mg/15 min, E2 4-hydroxylase activities were markedly elevated but, in the range of 50- 180 pmol/mg/15 min, statistically significant correlations again were not observed. Analysis also were performed on the relationships of E2 2- and 4-hydroxylations to BaP metabolism as assessed with high-pressure liquid chromatography (HPLC). Strong positive correlations were observed between quantities of nearly all measured BaP metabolites and 4-hydroxy- but not 2-hydroxy-E2. The threshold effect again was evident. E2 exhibited only weak activity as an inhibitor of placental BaP hydroxylation as measured fluorimetrically or with HPLC. BaP effectively inhibited E2 4-hydroxylase activities at comparatively low inhibitor concentrations but inhibited E2 2-hydroxylase activities only weakly. Analyses of the effects of a series of modifiers on the three measured mono-oxygenase activities also suggested that each activity was under separate regulatory control.