Molecular and cellular study of vasoactive physiological substance effects on the control mechanism of corpus luteum function

为阐明黄体功能的调控机制，本研究探讨了内皮素(ET)和一氧化氮(NO)对颗粒细胞(GC)黄体化和分泌期子宫内膜细胞分化的影响。结果表明，ET通过抑制导致孕酮产生的关键生物合成步骤抑制黄体生成，并诱导GC细胞增殖，提示黄体功能是一种局部因素。在未成熟卵泡中，NO/NOS抑制GC的黄体化，但在卵泡成熟过程中这种抑制作用减弱。NO还显著抑制基础状态和Gn刺激的PGC中雌二醇(E_2)的释放。我们还阐明了ET减少和内皮型一氧化氮合酶(NOS)增加之间的协同生物学效应，通过引起子宫内膜血管扩张，进而诱导分泌期子宫内膜细胞分化，从而参与调节子宫血流。提示ET和NO/NOS可能在黄体功能调控中起重要作用。

The present study was undertaken to investigate the effects of endothelin (ET), that is the potent vasoconstrictive peptide, and nitric oxide (NO) that is the free radical gas believed to be endothelium-derived relaxing factor on the luteinization in granulosa cells (GC) and on the differentiation in human endometrial cells of the secretory phase in order to clarify the control mechanism of luteal function.We have demonstrated that ET acts as a luteinization-inhibitor by attenuating key biosynthetic steps leading to progesterone production and induces the cell proliferation in GC, indicating the significant effects of luteal function as a local factor. NO/NOS suppresses the luteinization of GC in immature follicle, but the suppression decreases in the process of follicle maturation. NO also significantly suppressed the estradiol (E_2) release in basal and Gn-stimulated PGC. We also elucidate that the cooperative biological effects between the decrease in ET and the increase in endothelial NO synthase (NOS) contribute to the regulation of human uterine blood flow by causing dilatation of endometrial blood vessels, follwing to induce the differentiation in endometrial cells of secretory phase. These findings suggest that ET and NO/NOS may have a potential role in.the control of corpus luteum function.