In preovulatory ovarian follicles of mice, meiotic prophase arrest in the oocyte is maintained by cyclic GMP from the surrounding granulosa cells that diffuses into the oocyte through gap junctions. The cGMP is synthesized in the granulosa cells by the transmembrane guanylyl cyclase natriuretic peptide receptor 2 (NPR2) in response to the agonist C-type natriuretic peptide (CNP). In response to luteinizing hormone (LH), cGMP in the granulosa cells decreases, and as a consequence, oocyte cGMP decreases and meiosis resumes. Here we report that within 20. min, LH treatment results in decreased guanylyl cyclase activity of NPR2, as determined in the presence of a maximally activating concentration of CNP. This occurs by a process that does not reduce the amount of NPR2 protein. We also show that by a slower process, first detected at 2. h, LH decreases the amount of CNP available to bind to the receptor. Both of these LH actions contribute to decreasing cGMP in the follicle, thus signaling meiotic resumption in the oocyte.
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We thank Tracy Uliasz, Amber Selko, and Marilyn O’Brien for technical assistance, William Ratzan, Lisa Mehlmann, Jim Watras, and Deborah Dickey for their generous help, Viacheslav Nikolaev, Mark Terasaki, Michaela Kuhn, Dieter Müller, Jolanta Gutkowska, Matthew Movsesian, Claire Lugnier, Marina Freudzon, and Melina Schuh for stimulating discussions, and Joseph Burleson for statistical advice. This work was supported by grants R01 HD014939 to L.A.J. and U01 HD21970 to J.J.E., a grant from the National Basic Research Program of China (2012CB944401) to M.Z., a grant from the University of Minnesota Graduate School (21,922) to L.R.P., and NIH training grant T32AR050938 to J.W.R.
- Cyclic GMP
- Guanylyl cyclase
- Luteinizing hormone
- Mouse ovarian follicle