Inhibitory effects of interleukin-1 on luteinizing hormone-stimulated adenosine 3',5'-monophosphate accumulation by cultured porcine granulosa cells.
To elucidate the mechanisms of the inhibitory effect of interleukin-1 (IL-1) on LH-stimulated progesterone secretion by cultured porcine granulosa cells, we examined which steps of the LH-stimulated, cAMP-mediated, progesterone biosynthetic pathway were affected by IL-1. Pretreatment of the cells for 48 h with IL-1 reduced intra- and extracellular cAMP accumulation in response to LH by 73% and 83%, respectively. The inhibitory effects of IL-1 were time and concentration dependent. Significant inhibition was observed at as low as 50-250 pg/ml, and the effect was maximal at 100 ng/ml (ID50; 2 ng/ml). The lowest concentration of IL-1 used (0.5 pg/ml), in contrast, showed a tendency to stimulate LH-induced cAMP accumulation. Effect of IL-1 on the specific binding of [125I]LH to granulosa cells was then examined, which showed that IL-1 (100 ng/ml) significantly reduced the specific binding by 36%. IL-1 also significantly reduced intra- and extracellular cAMP accumulation by the cells in response to forskolin (50, 150 microM) by 28-46%, indicating that IL-1 can directly inhibit adenylate cyclase activity. Contrary to these inhibitory actions of IL-1 on LH-stimulated cAMP generation, IL-1 did not significantly reduce progesterone secretion induced by (Bu)2cAMP. These results indicate that the inhibitory effect of IL-1 on LH-stimulated progesterone secretion is due to its actions at at least two different sites along the LH-stimulated, cAMP-mediated, progesterone biosynthetic pathway, the LH receptor level and adenylate cyclase systems. The post-cAMP steps of progesterone production, in contrast, did not seem to be affected by IL-1.
Fukuoka
M
M
Department of Gynecology & Obstetrics, Faculty of Medicine, Kyoto University, Japan.
Taii
S
S
Yasuda
K
K
Takakura
K
K
Mori
T
T
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D006107:Granulosa Cells / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000378:metabolism / Q000494:pharmacology*; D011374:Progesterone / Q000378:metabolism; D013552:Swine
D007375:Interleukin-1; D005576:Colforsin; D011374:Progesterone; D003994:Bucladesine; D007986:Luteinizing Hormone; D000242:Cyclic AMP