Endocrinology, Vol 118, 1952-1960, Copyright © 1986 by Endocrine Society

ARTICLES

17 beta-estradiol 2- and 4-hydroxylation catalyzed by rat hepatic cytochrome P-450: roles of individual forms, inductive effects, developmental patterns, and alterations by gonadectomy and hormone replacement

GA Dannan, DJ Porubek, SD Nelson, DJ Waxman and FP Guengerich

The participation of rat hepatic P-450 in the conversion of 17 beta- estradiol to catechol estrogens was examined by means of enzyme reconstitution and immunoinhibition studies. It was thus demonstrated that three rat liver microsomal cytochrome P-450 forms, designated P- 450UT-A, P-450PCN-E, and P-450ISF-G, each contribute to the 2- and 4- hydroxylation of 17 beta-estradiol catalyzed by hepatic microsomal preparations. Two of these enzymes, P-450UT-A and P-450PCN-E, are expressed constitutively, are male-specific, and are regulated by testosterone as well as influenced by the administration of various chemicals. Consistent with these observations, 17 beta-estradiol 2- and 4-hydroxylation activities both increased rapidly during puberty in male rats and were induced by treatment of rats with phenobarbital or pregnenolone 16 alpha-carbonitrile. Castration of male rats at birth or at 5 weeks of age suppressed the levels of 17 beta-estradiol 2- and 4- hydroxylase activities measured at 10 weeks of age. This suppression of activity was reversed upon administration of testosterone during the neonatal period (days 1 and 3 of life) or by capsule implantation at 5 weeks of age. These patterns of 17 beta-estradiol 2- and 4- hydroxylation are discussed in terms of the previously characterized response of the multiple rat hepatic P-450 forms to ontogenic, hormonal, and xenobiotic factors.

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