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本文用离体细胞体外孵育法研究了内皮素-1(ET)对大鼠排卵前卵泡颗粒细胞孕酮生成的影响及其作用机理。结果发现,ET能显著抑制hCG刺激下的孕酮产生,抑制作用在浓度为10-8mol/L时,即有显著意义(P<0.05,n=6),至10-7mol/L时则有非常显著的意义(P<0.01,n=6);不同浓度ET(10-7—10-7mol/L),对颗粒细胞基础孕酮的产生无明显影响。进一步研究表明,ET对hCG刺激下孕酮生成的抑制作用,在用免抗人内皮素抗血清(ET-A)1:1000及cAMP后能明显被逆转。实验中还观察到,ET使颗粒细胞LH/hCG受体数下降,亲和力降低。本文结果提示,ET可能为卵巢内的一种局部调节肽,通过作用于ET受体,干扰LH/hCG受体功能和cAMP生成而抑制颗粒细胞孕酮的产生。
In this study, we investigated the effect of endothelin-1 (ET) on progesterone production in preovulatory follicle granulosa cells and its mechanism of action in vitro. The results showed that ET could significantly inhibit the production of progesterone induced by hCG, and the inhibitory effect was significant at the concentration of 10-8mol / L (P <0.05, n = 6) (P <0.01, n = 6). Different concentrations of ET (10-7-10-7 mol / L) had no significant effect on the basis progesterone production of granulosa cells. Further studies showed that the inhibitory effect of ET on progesterone production under hCG stimulation was reversed significantly after 1: 1000 anti-human endothelin antiserum (ET-A) and cAMP. The experiment also observed that ET decreased the number of LH / hCG receptors in granulosa cells and decreased the affinity. Our results suggest that ET may be a local regulatory peptide in the ovary that inhibits the production of progesterone in granulosa cells by acting on ET receptors and interfering with LH / hCG receptor function and cAMP production.