Coordinated induction of estrogen hydroxylase and catechol-O-methyl transferase by xenobiotics in first trimester human placental explants.
The estrogen phenol A-ring metabolism was investigated in the first trimester placenta using radioenzymatic techniques. In untested explants cultured for 16 h, estrogen hydroxylase (EH) but not catechol-O-methyl transferase (COMT) activity was increased significantly 1.8-fold (P less than 0.05). Cultures made in the presence of chemoprotectors, 25 microM of 1-phenylazo-2-naphthol (Sudan I) and coumarin but not 2(3)-tert-butyl-4-hydroxyanisole (BHA) caused a significant increase in EH activity, 1.8- and 2.2-fold, respectively (P less than 0.05). This was coupled with a significant, P less than 0.05, increase in the COMT activity by 25 microM of all three chemoprotectors, BHA, Sudan I, and coumarin, 2.7-, 2.3-, and 2-fold respectively. The carcinogens benzo(a)pyrene and 20-methylcholanthrene at 50 microM concentration, however, had no effect upon both enzymes' activity. Finally, the two enzymes's activities were correlated under the experimental conditions tested. Except for zero time where no correlation was found (r2 = 0.3), in all other experimental conditions, a significant (r2 = 0.75) correlation was observed. In conclusion, EH and COMT enzyme activities appear to undergo a coordinated induction in cultured placental explants in the first trimester. The implications of catechol metabolism for embryonal development are discussed.
Barnea
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Rappaport Institute, Technion Medical School, Rambam Medical Center, Departmetn of Ob/Gyn A., Haifa, Israel.
Avigdor
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D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D002273:Carcinogens; D002394:Catechol O-Methyltransferase / Q000096:biosynthesis*; D003374:Coumarins / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D009284:Naphthols / Q000494:pharmacology; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy / Q000378:metabolism*; D011261:Pregnancy Trimester, First; D013250:Steroid Hydroxylases / Q000096:biosynthesis*; D015262:Xenobiotics / Q000494:pharmacology*
D002273:Carcinogens; D003374:Coumarins; D009284:Naphthols; D015262:Xenobiotics; D002083:Butylated Hydroxyanisole; C024336:1-phenylazo-2-naphthol; D003577:Cytochrome P-450 Enzyme System; C030123:coumarin; D013250:Steroid Hydroxylases; D019363:Cytochrome P-450 CYP1A1; C020120:estrogen 2-hydroxylase; D002394:Catechol O-Methyltransferase