Regulation of Meiotic Arrest in Oocytes by G-Proteins

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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.