Acute decrease by human chorionic gonadotropin of the activity of preovulatory ovarian 17 alpha-hydroxylase and C-17-C-20 lyase is due to decrease of microsomal cytochrome P-450 through de novo synthesis of ribonucleic acid and protein.
Female rats were treated with 10 IU pregnant mare's serum gonadotropin (PMSG) on the 21st day after birth, and 53 h later with 20 IU human CG (hCG) in order to investigate the mechanism of action of hCG upon ovarian 17 alpha-hydroxylase and C-17-C-20 lyase. The activity of ovarian 17 alpha-hydroxylase and C-17-C-20 lyase was severely decreased within 6 h after the injection of hCG. However, treatment with cycloheximide or puromycin before the hCG injection prevented the decrease in the activity of these enzymes by hCG. Actinomycin D pretreatment prevented the hCG-induced decrease of C-17-C-20 lyase activity. In correlation with the changes in these enzyme activities induced by hCG, the concentration of ovarian microsomal cytochrome P-450 decreased to barely detectable level after hCG treatment; this decrease was also prevented by pretreatment with cycloheximide. When the cytochrome P-450 obtained from the PMSG-treated rats was subjected to spectrometric analysis of binding with progesterone and 17 alpha-hydroxy-progesterone, type I spectra were obtained for both steroids, indicating that the steroids bound to the cytochrome as substrate. Testosterone, a substrate for aromatase, showed very limited binding to the cytochrome, however. On the other hand, the microsomes obtained from the PMSG + hCG treated ovaries showed no type I spectrum with progesterone and 17 alpha-hydroxy-progesterone. The activity of NADPH-cytochrome c reductase in the ovarian microsomes was not significantly influenced by the hCG treatment. These results indicate that the acute decrease of ovarian 17 alpha-hydroxylase and C-17-C-20 lyase activity by hCG treatment was caused through the decrease of cytochrome P-450 and is correlated with de novo synthesis of RNA and protein.
D000446:Aldehyde-Lyases / Q000378:metabolism*; D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D007700:Kinetics; D008861:Microsomes / Q000201:enzymology*; D010053:Ovary / Q000187:drug effects / Q000201:enzymology*; D010060:Ovulation; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism*; D013250:Steroid Hydroxylases / Q000378:metabolism*; D013256:Steroids / Q000096:biosynthesis
D006063:Chorionic Gonadotropin; D013256:Steroids; D012313:RNA; D003577:Cytochrome P-450 Enzyme System; D003513:Cycloheximide; D013250:Steroid Hydroxylases; D013254:Steroid 17-alpha-Hydroxylase; D000446:Aldehyde-Lyases