Calcium dependence of the inhibitory effect of gonadotropin-releasing hormone on luteinizing hormone-induced cyclic AMP production in rat granulosa cells.
The role of calcium in the inhibitory action of the GnRH superagonist, [D-Ala6]des-Gly10-GnRH N-ethylamide (GnRHa), on LH-stimulated cAMP production was studied in cultured granulosa cells obtained from immature hypophysectomized diethylstilbestrol (DES)-implanted rats. After culture for 48 h with FSH to induce LH receptors, cells were incubated for 2 h with LH or LH plus GnRHa. In this system, the cAMP response to LH was independent of extracellular calcium. In the presence of 0.25 to 1 mM extracellular calcium, 10(-8) M GnRHa caused a 15 to 40% inhibition of LH-stimulated cAMP production. Omission of extracellular calcium completely abolished the inhibitory effect of GnRHa upon LH-induced cAMP production. The inhibitory effects of GnRHa on prostaglandin E2 (PGE2) and isoproterenol-induced cAMP productions were also markedly reduced in the absence of extracellular calcium. Addition of the phosphodiesterase inhibitor, 1-methyl-3-isobutylxanthine (MIX), reversed the inhibitory action of GnRHa on LH-induced cAMP production. These results demonstrate that extracellular calcium is necessary for the acute inhibitory action of GnRHa upon LH-induced cAMP production in cultured rat granulosa cells, and indicate that increased degradation of cAMP may be a contributing factor for this effect of GnRHa.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D004054:Diethylstilbestrol / Q000494:pharmacology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D007016:Hypophysectomy; D007986:Luteinizing Hormone / Q000494:pharmacology*; D051381:Rats
D007987:Gonadotropin-Releasing Hormone; D004054:Diethylstilbestrol; D007986:Luteinizing Hormone; D000242:Cyclic AMP; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine