Regulation of Meiotic Arrest in Oocytes by G-Proteins

描述（由申请方提供）：哺乳动物卵母细胞在卵泡内生长和成熟。它们在减数分裂的前期I被阻止，直到它们达到它们的完整大小，并且响应于排卵前促黄体激素（LH）的激增，它们被刺激恢复减数分裂。卵母细胞周围卵泡细胞的存在是维持减数分裂停滞所必需的，并且这种停滞似乎是由卵母细胞中cAMP的升高介导的。然而，卵泡和卵母细胞之间的信号传导途径还不清楚。最近的证据表明，刺激腺苷酸环化酶的Gs G蛋白在维持减数分裂停滞中的作用。然而，目前尚不清楚Gs活性是如何在卵母细胞中维持的，或者LH对卵泡细胞的作用是如何启动减数分裂的恢复的。该提议的具体目的是：1）鉴定卵母细胞中可能负责刺激Gs的Gs偶联受体蛋白; 2）测试小鼠卵母细胞中发现的任何Gs相关受体的功能; 3）检查LH是否可能通过刺激卵母细胞中的Gi G蛋白而触发卵母细胞成熟，从而关闭cAMP的产生。了解卵泡内卵母细胞的细胞周期是如何调节的，可能会应用于实际问题，包括辅助生殖技术，避孕和不孕症。

DESCRIPTION (provided by applicant): Mammalian oocytes grow and mature within ovarian follicles. They are arrested at prophase I of meiosis until they reach their full size, and in response to a preovulatory surge of luteinizing hormone (LH), they are stimulated to resume meiosis. The presence of the follicle cells around the oocyte is necessary to maintain meiotic arrest, and the arrest appears to be mediated by elevation of cAMP in the oocyte. However, the signaling pathways between the follicle and the oocyte are not well understood. Rece nt evidence points to a role for the Gs G-protein, which stimulates adenylyl cyclase, in maintaining meiotic arrest. However, it is not yet known how Gs activity is maintained in the oocyte, or how LH action on the follicle cells initiates the resumption of meiosis. The specific aims of this proposal are: 1) to identify Gs-coupled receptor proteins in the oocyte that may be responsible for stimulating Gs; 2) to test the function of any Gs-linked receptors that are found in the mouse oocyte; and 3) to examine whether LH might trigger oocyte maturation by stimulating a Gi G-protein in the oocyte, thus turning off the production of cAMP. Understanding how the oocyte cell cycle is regulated within the follicle may find applications to practical problems including assisted reproductive techniques, contraception, and infertility.