Regulation of Meiotic Arrest in Oocytes by G-Proteins

描述（由申请人提供）：哺乳动物卵母细胞在卵巢卵泡内生长和成熟。它们在减数分裂的前期被抑制，直到它们达到完全的大小，并且在排卵前黄体生成素（LH）激增的反应下，它们被刺激恢复减数分裂。卵泡细胞在卵母细胞周围的存在是维持减数分裂停滞所必需的，而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通路尚不清楚。越来越多的证据表明，刺激腺苷酸环化酶的g - g蛋白在维持减数分裂停滞中起着重要作用。然而，目前尚不清楚Gs活性如何在卵母细胞中维持，以及LH作用于卵泡细胞如何启动减数分裂的恢复。本提案的具体目的是：1)鉴定卵母细胞中可能负责刺激Gs的Gs偶联受体蛋白；2)测试在小鼠卵母细胞中发现的任何gs连接受体的功能；3)检查LH是否可能通过刺激卵母细胞中的Gi - g蛋白，从而关闭cAMP的产生，从而触发卵母细胞成熟。了解卵泡内卵母细胞周期是如何调节的，可能会在辅助生殖技术、避孕和不孕等实际问题上找到应用。

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.