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The effect of endothelin-1 (ET) on progesterone production of isolated rat granulosa cells and its mechanism were investigated. ET could inhibit the hCG-stimulated progesterone production significantly at the concentration of 10(-8) mol/L (P < 0.05, n = 6) and highly significantly at the concentration of 10(-7) mol/L (P < 0.05, n = 6), but ET did not inhibit the basal progesterone production at various concentrations (10(-10)-10(-7) mol/L). Further experiments showed that the inhibitory effect of ET on the hCG-stimulated progesterone production could be reversed by rabbit antiserum to ET (ET-A, 1:1000) or cAMP (10(5) mol/L). ET could decrease the binding sites and the affinity constant (ka) of LH/hCG receptor on granulosa cells. All these findings suggest that ET may be an intraovarian regulatory factor which may inhibit progesterone production stimulated by hCG from rat granulosa cells through inerfering LH/hCG receptor function and cAMP formation.
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