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Gossypolone suppresses progesterone synthesis in bovine luteal cells |
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| Authors: | Y Gu PK Li YC Lin Y Rikihisa RW Brueggemeier |
| Institution: | a Laboratory of Reproductive Endocrinology, Department of Veterinary Physiology and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH 43210-1092, U.S.A. b Department of Veterinary Pathobiology, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210-1092, U.S.A. c Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210-1092, U.S.A. |
| Abstract: | 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 3β-hydroxysteroid dehydrogenase (3β-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 μM) induced morphological changes in cellular organelles. |
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