Regulation of Meiotic Arrest in Oocytes by G-Proteins

G 蛋白对卵母细胞减数分裂停滞的调节

• 批准号: 6758536
• 负责人: LISA M MEHLMANN
• 金额: $ 7.25万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6758536
• 关键词: G protein; biological signal transduction; cyclic AMP; egg /ovum; genetically modified animals; hormone regulation /control mechanism; immunofluorescence technique; laboratory mouse; luteinizing hormone; meiosis; polymerase chain reaction; protein structure function; receptor coupling; tissue /cell culture

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.

描述（由申请人提供）：哺乳动物卵母细胞在卵巢卵泡中生长和成熟。它们在减数分裂的先前被捕，直到达到全尺寸为止，并且为了响应叶酸激素（LH）的排卵前激增，它们被刺激以恢复减数分裂。卵母细胞周围的卵泡细胞的存在是维持减数分裂逮捕的必要条件，并且该逮捕似乎是由卵母细胞升高的升高而介导的。但是，卵泡和卵母细胞之间的信号传导途径尚不清楚。接收证据表明，GS G蛋白的作用，该GS G蛋白刺激腺苷酸环化酶在维持减数分裂骤停中的作用。但是，尚不清楚如何在卵母细胞中保持GS活性，或者在卵泡细胞上的LH作用如何引发减数分裂的恢复。该提案的具体目的是：1）识别卵母细胞中可能负责刺激GS的GS耦合受体蛋白； 2）测试小鼠卵母细胞中发现的任何GS连接受体的功能； 3）检查LH是否会通过刺激卵母细胞中的Gi G蛋白来触发卵母细胞的成熟，从而关闭CAMP的生产。了解如何在卵泡中调节卵母细胞周期，可能会在包括辅助生殖技术，避孕和不育症等实际问题上找到应用。