The cytochrome P450(17) alpha (17 alpha-hydroxylase/C17,20-lyase) activity of the junctional zone of the rat placenta.
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 P450(17) alpha, 17 alpha-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; 10 IU 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Johnson
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Department of Gynecology & Obstetrics, Ralph L. Smith Research Center, University of Kansas Medical Center, Kansas City 66103.
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D000022:Abortion, Spontaneous / Q000139:chemically induced; D000446:Aldehyde-Lyases / Q000378:metabolism*; D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D007016:Hypophysectomy; D007986:Luteinizing Hormone / Q000494:pharmacology; D010053:Ovary / Q000187:drug effects / Q000201:enzymology; D010920:Placenta / Q000187:drug effects / Q000201:enzymology*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism*; D013250:Steroid Hydroxylases / Q000378:metabolism*
D006063:Chorionic Gonadotropin; D007986:Luteinizing Hormone; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D013254:Steroid 17-alpha-Hydroxylase; D000446:Aldehyde-Lyases