Catechol estrogen formation in the mouse uterus and its role in implantation.
Estradiol-2/4-hydroxylase (E-2/4-H) activity was determined in the mouse uterus during early pregnancy as well as in ovarian steroid hormone-treated ovariectomized uterus. Under the assay conditions used, E-4-H was the predominant catechol estrogen-forming monooxygenase enzyme. The inhibition of E-4-H activity by SKF-525A, metyrapone and alpha-naphthoflavone suggested involvement of cytochrome P450-dependent monooxygenases. A haloestrogen, 2-fluoroestradiol (2-FL-E2), also inhibited this activity. During the peri-implantation period, no change in uterine E-4-H activity was noted on the morning of days 2 through 5, but the activity significantly (P less than 0.01) increased in the afternoon of day 4 of pregnancy. A single injection of estradiol-17 beta (E2, 100 ng/mouse) to ovariectomized mice significantly (P less than 0.01) elevated the level of E-4-H activity at 24 h as did injections of progesterone (P4, 2 mg/mouse) for 2 days. When 2 days of P4 (2 mg/mouse) treatment was combined with a single injection of E2 (20 ng/mouse), E-4-H activity increased 1.3-fold (P less than 0.05) by 24 h above that of P4 treatment alone. Dexamethasone (200 micrograms/mouse) and cholesterol (2 mg/mouse) treatment for 2 days had no effect on E-4-H activity. Thus, the stimulatory effect of P4 and E2 on E-4-H activity appeared to be specific. The increased activity of uterine E-4-H prior to implantation on day 4 evening and the modulation of its activity by P4 and/or E2 suggest an involvement of 4-hydroxyestradiol in embryo implantation.(ABSTRACT TRUNCATED AT 250 WORDS)
Paria
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Department of Obstetrics and Gynecology and Physiology, University of Kansas Medical Center, Ralph L. Smith Research Center, Kansas City 66103.
Chakraborty
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Dey
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D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D002851:Chromatography, High Pressure Liquid; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology; D010064:Embryo Implantation / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D002393:Estrogens, Catechol / Q000096:biosynthesis*; D005260:Female; D007700:Kinetics; D051379:Mice; D010052:Ovariectomy; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology; D013250:Steroid Hydroxylases / Q000378:metabolism*; D014599:Uterus / Q000378:metabolism*
D002393:Estrogens, Catechol; C037475:2-fluoroestradiol; D011374:Progesterone; D004958:Estradiol; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C585498:Cyp1b1 protein, mouse; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; C020120:estrogen 2-hydroxylase; D015232:Dinoprostone