NO AND CYCLIC GMP EFFECTS ON GRANULOSA CELL FUNCTIONS

生殖能力的建立和维持依赖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诱导颗粒细胞功能成熟，与雌二醇（E2）产生增加相关。除了FSH的作用外，颗粒细胞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。我们最近已经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诱导的芳香化酶活性的抑制作用。颗粒细胞与NO发生器孵育抑制FSH刺激的雌二醇（E2）合成，与环GMP水平增加有关。有趣的是，用环GMP类似物处理颗粒细胞模拟NO对E2水平的抑制作用，表明NO作用的机制，并证明环GMP对E2产生的拮抗作用。我们最近的研究结果表明，NO也减弱FSH刺激的颗粒细胞，NO和环GMP的类固醇激素合成和信号转导在大鼠颗粒细胞中的环AMP水平。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，关于卵巢中PDE的调节表达知之甚少。因此，建议FSH对颗粒细胞的成熟。这些研究的结果将提供关于no，环GMP和PDE在卵巢功能中的作用的重要新信息，并将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.