Cellular localization and factors controlling rat placental cytochrome P45017 alpha (CYP17): 17 alpha-hydroxylase/C17,20-lyase activity.
The junctional zone of the rat placenta, during the second half of gestation, contains cytochrome P45017 alpha (CYP17), the enzyme responsible for androgen synthesis. The present study was undertaken to 1) determine the cellular source of this enzyme and 2) examine the effect of various hormones upon the activity of the enzyme. An antiserum to a 15-amino-acid peptide, representing the carboxyl terminus of rat testicular CYP17, was raised in rabbits. This antiserum inhibited the activity of rat ovarian microsomal C17,20-lyase and reacted with a microsomal protein of about 55 kDa from ovarian and placental homogenates on Western immunoblots. When used for immunohistochemistry the antibody stained only the trophoblastic giant cells of the Day 15 (sperm-positive Day 1) rat placenta; not all giant cells were stained to the same extent and not all cells were stained. Removal of the hypophysis on Day 3 of pregnancy, and delay of implantation, resulted in increased placental C17,20-lyase activity in NIMR/AS dwarf--which lack only growth hormone--but not in normal Holtzman strain rats. Growth hormone, prolactin, testosterone propionate, excess progesterone, or withholding estrogen had no significant effect upon the specific activity of the placental enzyme. In contrast, increases in serum estradiol, produced endogenously by hCG or LH, or exogenously by silastic capsules containing diethylstilbestrol or estradiol-17 beta, significantly reduced enzyme activity. The results indicate that trophoblastic giant cells of the chorioallantoic and choriovitelline placentas contain the androgen-synthesizing enzyme system of the rat placenta and that this system is exquisitely sensitive to inhibition by estrogen.
Johnson
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Department of Gynecology & Obstetrics, Ralph L. Smith Research Center, University of Kansas Medical Center, Kansas City 66103.
D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D005260:Female; D015726:Giant Cells / Q000201:enzymology; D007016:Hypophysectomy; D007150:Immunohistochemistry; D007986:Luteinizing Hormone / Q000494:pharmacology; D008861:Microsomes / Q000201:enzymology; D010920:Placenta / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D011247:Pregnancy; D051381:Rats; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism*
D006063:Chorionic Gonadotropin; D007986:Luteinizing Hormone; D013254:Steroid 17-alpha-Hydroxylase