NO AND CYCLIC GMP EFFECTS ON GRANULOSA CELL FUNCTIONS

生殖能力的建立和维持取决于多种因素对卵巢的影响。卵巢功能受垂体促性腺激素、促卵泡激素（FSH）和促黄体激素（LH）的高度调节。FSH通过第二信使环AMP诱导颗粒细胞的功能成熟，与雌二醇（E2）的产生增加有关。除了FSH的作用外，颗粒细胞的成熟还受到其他激素和酶的调节，这些激素和酶通过不同的信号转导途径起作用。我们最近证明了可溶性鸟苷酸环化酶的主要激活剂一氧化氮（NO）对fsh诱导的芳香酶活性的抑制作用。颗粒细胞与NO发生器孵育抑制FSH刺激雌二醇（E2）合成，与环GMP水平升高相关。有趣的是，用环GMP类似物处理颗粒细胞模拟了NO对E2水平的抑制作用，这表明NO的作用机制，并证明了环GMP对E2产生的拮抗作用。我们最近的研究结果表明，NO还能减弱fsh刺激的颗粒细胞中环AMP的水平，NO和环GMP对大鼠颗粒细胞中类固醇生成和信号转导的影响。然而，NO和环GMP抑制fsh诱导的E2和环AMP水平的机制尚不清楚。此外，PDEs在卵巢中的调控表达尚不清楚。因此，FSH对颗粒细胞成熟的影响被提出。这些研究结果将为no、环GMP和PDEs在卵巢功能中的作用提供重要的新信息，并可能导致与避孕和不孕症治疗相关的新临床方法。

The establishment and maintenance of reproductive competence is dependent upon the influences of many factors act on the ovary. Ovarian functions are highly regulated by the pituitary gonadotropins, follicle- stimulating hormone (FSH) and luteinizing hormone (LH). FSH acts through the second messenger cyclic AMP to induce functional maturation of granulosa cells, associated with increased production of estradiol (E2). In addition to the effects of FSH, granulosa cell maturation is also modulated by other hormones and enzymes, which act through different signal transduction pathways. We have recently demonstrated the inhibitory influences of the major activator of soluble guanylate cyclase, nitric oxide (NO), on FSH-induced aromatase activity. Incubation of granulosa cells with generators of NO inhibits FSH- stimulated estradiol (E2) synthesis, associated with increased levels of cyclic GMP. Interestingly, treatment of granulosa cells with cyclic GMP analogs mimics the inhibitory effects of NO on E2 levels, suggesting a mechanism of NO action and demonstrating the antagonistic effect of cyclic GMP on E2 production. Our most recent findings indicate that NO also attenuates FSH-stimulate cyclic AMP levels in granulosa cells, NO and cyclic GMP on steroidogenesis and signal transduction in rat granulosa cells. However, the mechanisms by which NO and cyclic GMP inhibit FSH-induced E2 and cyclic AMP levels are not known. In addition, little is known regarding the regulated expression of PDEs in the ovary. Therefore, the proposal of FSH on granulosa cell maturation. The findings from these studies will provide important new information regarding the roles of no, cyclic GMP, and PDEs in ovarian functions, and my lead to new clinical approaches related to contraception and infertility treatment.