The cytochrome P45017α (17α-hydroxylase/C17,20-lyase) activity of the junctional zone of the rat placenta

Abstract

ABSTRACT The cytochrome P450 responsible for androgen synthesis by the placenta during the second half of pregnancy in the rat was studied in intact and hypophysectomized animals. The two activities of P45017α, 17α-hydroxylase and C17,20-lyase, were limited to the junctional zone. C17,20-Lyase activity was greater with progesterone than with 17-hydroxyprogesterone as substrate. Although the apparent Michaelis constants were similar, progesterone had a higher maximum velocity than 17-hydroxyprogesterone. Regardless of substrate, C17,20-lyase activity was greater with NADPH than with NADH as an electron donor, and there was no additive effect using both cofactors. Administration of human chorionic gonadotrophin (hCG; 10IU at 09.00 and 21.00 h on days 13 and 14 and at 09.00 h on day 15) to intact females resulted in more than a 50% reduction of enzyme activity when measured on day 15. The same dose of hCG given to hypophysectomized animals with delayed implantation, i.e. pituitary removal on day 3 and implantation induced by oestrone 5 days later, had no effect on placental enzyme activity, but increased that in the ovary. Administration of ovine LH by osmotic minipump (days 11–15) to intact females resulted in abortion in all animals. The same treatment to animals hypophysectomized on day 11 produced abortion in three of four rats; enzyme activity was greatly reduced in the single animal with placentas. In contrast, infusion of LH into hypophysectomized animals with delayed implantation increased placental enzyme activities. However, administration of 20IU pregnant mare's serum gonadotrophin to the hypophysectomized animals on day 11 produced a large increase in ovarian follicular development and ovarian P45017α activities, and resulted in abortion in three of five animals within 96 h. The results indicate that the P45017α of the junctional zone of the rat placenta has characteristics similar, if not identical, to those of the ovary with regard to preference of substrate and electron donor. However the enzyme activity in the placenta did not increase to the same extent as that in the ovary when exposed to gonadotrophins with LH activity, suggesting that the control mechanisms may be different. Journal of Endocrinology (1990) 125, 217–224