Inhibition of follicle-stimulating hormone- and adenosine-3',5'-cyclic monophosphate-induced progesterone production by calcium and protein kinase C in the rat ovary.
In this study we examined the effects of A23187 (a calcium ionophore) and 12-O-tetradecanoyl phorbol-13-acetate, a known activator of protein kinase C, on progesterone production. Granulosa cells obtained from pregnant mare serum gonadotropin-primed rats were maintained in primary culture. Treatment with follicle-stimulating hormone (0.5 microgram/ml), 8-bromo-adenosine-3',5'-cyclic monophosphate (2 mmol/L), or cholera toxin (0.1 microgram/ml) for 5 hours or 24 hours markedly stimulated progesterone production. The concomitant presence of A23187 attenuated the elevated levels of progesterone induced by follicle-stimulating hormone, 8-bromo-adenosine-3',5'-cyclic monophosphate, or cholera toxin, with or without the presence of a phosphodiesterase inhibitor, 1-methyl-3-isobutylxanthine (0.2 mmol/L). Likewise, treatment of the cells with 12-O-tetradecanoyl phorbol-13-acetate suppressed follicle-stimulating hormone-induced progesterone production, whether or not 1-methyl-3-isobutylxanthine was present in the cultures. The effect of 12-O-tetradecanoyl phorbol-13-acetate was not mimicked by phorbol-13-monoacetate or 4 alpha-phorbol-12, 13-didecanoate. These results indicate that both A23187 and 12-O-tetradecanoyl phorbol-13-acetate inhibit follicle-stimulating hormone-induced progesterone production, in part at a step or steps beyond adenosine-3',5'-cyclic monophosphate generation and degradation. They further support a role of calcium and protein kinase C in the intraovarian action of luteinizing hormone-releasing hormone.
Leung
P C
PC
Department of Obstetrics and Gynaecology, University of British Columbia, Grace Hospital, Vancouver, Canada.
Minegishi
T
T
Wang
J
J
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D006107:Granulosa Cells / Q000378:metabolism*; D011374:Progesterone / Q000096:biosynthesis*; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015124:8-Bromo Cyclic Adenosine Monophosphate; D000001:Calcimycin; D011374:Progesterone; D005640:Follicle Stimulating Hormone; D002772:Cholera Toxin; D000242:Cyclic AMP; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium