Catecholoestrogen synthesis and metabolism in the rabbit uterus during the periimplantation period.
Microsomal oestradiol-2/4-hydroxylase (OE-2/4-H) and cytosolic catechol-O-methyltransferase (COMT) (EC 2.1.1.6) activity in the uteri of pregnant and pseudopregnant rabbits during the periimplantation period were studied. The apparent Km for the 4-hydroxylation of oestradiol (3.18 microM) was considerably less than for the 2-hydroxylation reaction (13.36 microM), whereas the Vmax were almost equal. This suggests that 4-hydroxyoestradiol (4-OH-OE2) is the predominant product of OE-2/4-H in the rabbit uterus. These reactions were inhibited by SKF-525A, indicating the involvement of cytochrome P450 dependent monooxygenases. Uterine cytosolic COMT utilized 2-hydroxyestradiol (2-OH-OE2) as the preferred substrate as compared to 4-hydroxyoestradiol (4-OH-OE2). Since the rabbit uterus has a considerable capacity to synthesize 4-OH-OE2 and a lower capacity to metabolize it, it could be suggested that more 4-OH-OE2 than 2-OH-OE2 could be available to the uterus for its physiological activities. Furthermore, an increase in OE-2/4-H in Day 6 pseudopregnant and pregnant uteri with a concomitant decrease in COMT suggests the involvement of catecholoestrogens in the implantation process in the rabbit.
Chakraborty
C
C
Department of Obstetrics/Gynecology and Physiology, University of Kansas Medical Center, Ralph L. Smith Research Center, Kansas City 66103.
Huet-Hudson
Y M
YM
Dey
S K
SK
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D003600:Cytosol / Q000201:enzymology; D010064:Embryo Implantation / Q000502:physiology*; D004958:Estradiol / Q000031:analogs & derivatives / Q000378:metabolism; D002393:Estrogens, Catechol / Q000096:biosynthesis* / Q000378:metabolism; D005260:Female; D008861:Microsomes / Q000201:enzymology; D011247:Pregnancy; D011555:Pseudopregnancy / Q000378:metabolism; D011817:Rabbits; D013250:Steroid Hydroxylases / Q000378:metabolism; D013379:Substrate Specificity; D014599:Uterus / Q000378:metabolism*
D002393:Estrogens, Catechol; D004958:Estradiol; C001390:2-hydroxyestradiol; C014036:4-hydroxyestradiol; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; C020120:estrogen 2-hydroxylase; D002394:Catechol O-Methyltransferase