Gossypolone suppresses progesterone synthesis in bovine luteal cells.
Gossypolone, a proposed major metabolite of gossypol, was synthesized and investigated for its effect on progesterone synthesis in cultured bovine luteal cells. Gossypolone inhibited human chorionic gonadotropin(hCG)-stimulated progesterone secretion, reduced substrate-enhanced conversions of 25-hydroxycholesterol to pregnenolone and of pregnenolone to progesterone in a dose-dependent fashion. These findings indicate that gossypolone inhibits not only 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity, as gossypol does, but also side-chain cleavage enzyme complex (cytochrome P450scc) activity. However, the two compounds appear to have a similar potency in inhibiting progesterone secretion. Both gossypolone and gossypol (8.5 microM) induced morphological changes in cellular organelles.
Gu
Y
Y
Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Ohio State University, Columbus 43210-1092.
Li
P K
PK
Lin
Y C
YC
Rikihisa
Y
Y
Brueggemeier
R W
RW
D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000037:antagonists & inhibitors; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D005260:Female; D006072:Gossypol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006888:Hydroxycholesterols / Q000378:metabolism; D008184:Luteal Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D011284:Pregnenolone / Q000378:metabolism; D011374:Progesterone / Q000096:biosynthesis*
D006063:Chorionic Gonadotropin; D006888:Hydroxycholesterols; C043259:gossypolone; D011374:Progesterone; D011284:Pregnenolone; C007997:25-hydroxycholesterol; D015096:3-Hydroxysteroid Dehydrogenases; D002786:Cholesterol Side-Chain Cleavage Enzyme; D006072:Gossypol