Mono-oxygenase induction in the human placenta. Interrelationships among position-specific hydroxylations of 17 beta-estradiol and benzo[a]pyrene.
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.
D000818:Animals; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000378:metabolism*; D001665:Binding Sites; D004790:Enzyme Induction; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D006801:Humans; D006900:Hydroxylation; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008861:Microsomes / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D011817:Rabbits; D012907:Smoking
D001580:Benzopyrenes; D001564:Benzo(a)pyrene; D004958:Estradiol; D006899:Mixed Function Oxygenases