title: G beta gamma signaling reduces intracellular cAMP to promote meiotic progression in mouse oocytes.
abstract: In nearly every vertebrate species, elevated intracellular cAMP maintains oocytes in prophase I of meiosis. Prior to ovulation, gonadotropins trigger various intra-ovarian processes, including the breakdown of gap junctions, the activation of EGF receptors, and the secretion of steroids. These events in turn decrease intracellular cAMP levels in select oocytes to allow meiotic progression, or maturation, to resume. Studies suggest that cAMP levels are kept elevated in resting oocytes by constitutive G protein signaling, and that the drop in intracellular cAMP that accompanies maturation may be due in part to attenuation of this inhibitory G protein-mediated signaling. Interestingly, one of these G protein regulators of meiotic arrest is the Galpha(s) protein, which stimulates adenylyl cyclase to raise intracellular cAMP in two important animal models of oocyte development: Xenopus leavis frogs and mice. In addition to G(alpha)(s), constitutive Gbetagamma activity similarly stimulates adenylyl cyclase to raise cAMP and prevent maturation in Xenopus oocytes; however, the role of Gbetagamma in regulating meiosis in mouse oocytes has not been examined. Here we show that Gbetagamma does not contribute to the maintenance of murine oocyte meiotic arrest. In fact, contrary to observations in frog oocytes, Gbetagamma signaling in mouse oocytes reduces cAMP and promotes oocyte maturation, suggesting that Gbetagamma might in fact play a positive role in promoting oocyte maturation. These observations emphasize that, while many general concepts and components of meiotic regulation are conserved from frogs to mice, specific differences exist that may lead to important insights regarding ovarian development in vertebrates.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology and Metabolism, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75390-8857, USA.
authors.forename: Arvind
authors.initials: A
authors.lastname: Gill
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Hammes
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D044387:GTP-Binding Protein beta Subunits / Q000502:physiology*; D044388:GTP-Binding Protein gamma Subunits / Q000502:physiology*; D007424:Intracellular Fluid / Q000378:metabolism / Q000502:physiology; D008540:Meiosis / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009865:Oocytes / Q000378:metabolism*
chemical_list: D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D000242:Cyclic AMP