Gonadotropin stimulation of pregnenolone metabolism in Chinese hamster ovary cells in culture.
To determine if Chinese Hamster Ovary (CHO) cells in culture are able to metabolize steroids, CHO cells were incubated in defined medium with [14C]pregnenolone. As shown, [14C]pregnenolone is metabolized to progesterone and other delta 53 beta steroids; this steroidogenic response is appreciably enhanced upon exposure of the cells to 50 nM gonadotropins (human chorionic gonadotropin and follicle-stimulation hormone). The primary metabolites that accumulate in the medium upon treatment with gonadotropins are 16 alpha-hydroxy-pregnenolone and 16 alpha-17 beta-dihydroxydehydroepiandrosterone. Exposure of the CHO cells to gonadotropins induces significant increases in the activities of 16 alpha-hydroxylase, 17 alpha-hydroxylase, and 17-20 lyase. Similar results are obtained when the CHO cells are treated with 0.1 mM 8-bromocyclic AMP, indicating that the gonadotropin enhancement of steroid metabolism is a cyclic AMP-mediated process. CHO cells apparently lack the cholesterol desmolase complex since 14C-cholesterol is not utilized by these cells to produce other steroid metabolites. These results indicate that CHO cells offer an in vitro system for the study of certain aspects of gonadotropin stimulation of steroidogenesis.
D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D006224:Cricetinae; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D010053:Ovary; D011284:Pregnenolone / Q000378:metabolism*; D039181:Steroid 16-alpha-Hydroxylase; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000378:metabolism
D006063:Chorionic Gonadotropin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D011284:Pregnenolone; D005640:Follicle Stimulating Hormone; D002784:Cholesterol; D000242:Cyclic AMP; D015096:3-Hydroxysteroid Dehydrogenases; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; D039181:Steroid 16-alpha-Hydroxylase; D013254:Steroid 17-alpha-Hydroxylase