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.