NO AND CYCLIC GMP EFFECTS ON GRANULOSA CELL FUNCTIONS

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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.