一氧化氮(NO)可调节多种细胞的发育，且对生殖功能有重要作用，然而其调节卵巢细胞发育的机制并不清楚。前期结果表明，T3联合FSH可提高颗粒细胞NOS3的蛋白含量并促进腔前卵泡生长，且通过Src/PI3K/Akt通路调节细胞发育。另外，甲状腺素[TH (T3和T4)]分泌失调会导致机体生殖内分泌紊乱，从而使卵泡发育受阻，还可影响卵巢细胞NOS(nitric oxide synthase)表达。然而NO是否介导TH调节卵巢细胞增殖及凋亡进而影响卵泡发育尚不清楚。在前期研究基础上，本课题利用体外卵泡、颗粒细胞培养模型，以NOS为切入点，研究卵泡发育过程中TH对卵巢细胞NOS表达及下游信号通路的调节，从而进一步探明NO在激素调节卵泡发育过程中的作用机理。通过这些研究最终阐明NO和TH调节卵泡发育的初步分子机制，研究结果对改善、治疗甲状腺机能紊乱引起的卵巢功能障碍具有一定的意义。

NO (Nitric Oxide) regulates cell development through different signaling pathways in the different cell types. Although NO plays an important role in the normal reproduction function, the mechanisms involved have not been elucidated. Our preliminary studies indicate that the combination of T3 and FSH increase NOS3 protein content and induce preantral follicle growth in vitro. Meanwhile, T3 and FSH induced granulosa cell development via Src/PI3K/Ak pathway. Dysregulation of TH [TH (T3 and T4)] support induces disorder of reproductive endocrinology, which is associated with impaired follicular development. In addition, hypo- and hyper-thyroidism modified NOS (nitric oxide synthase) content in rat ovary. However, whether TH promotes ovarian follicle growth through regulating ovarian cells proliferation and apoptosis, which is mediated by NO, is unclear. The overall objective of this program is to improve our understanding on the cellular and molecular mechanisms by which TH and NO regulate ovarian follicle growth, and specifically on the expression of NOS intermediates in the regulation of follicle destiny during follicular development base on the previous study. The present study will use follicle and granulosa cell culture system in vitro. These findings will advance the current understanding on the role of TH and NO in the regulation of reproductive function and provide important insight into improving and curing the ovarian dysfunction in the condition of TH dysregulation.