Luteinizing hormone reduces the activity of the NPR2 guanylyl cyclase in mouse ovarian follicles, contributing to the cyclic GMP decrease that promotes resumption of meiosis in oocytes

• Published in: Developmental biology Vol. 366; no. 2; pp. 308 - 316
• Main Authors: Robinson, Jerid W., Zhang, Meijia, Shuhaibar, Leia C., Norris, Rachael P., Geerts, Andreas, Wunder, Frank, Eppig, John J., Potter, Lincoln R., Jaffe, Laurinda A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.06.2012
• Subjects: agonists; Animals; Atrial natriuretic peptide; C-Type natriuretic peptide; Cyclic GMP; Cyclic GMP - metabolism; Female; Follicles; Gap junctions; Granulosa cells; Granulosa Cells - metabolism; Guanylate cyclase; Guanylyl cyclase; Luteinizing hormone; Luteinizing Hormone - metabolism; Luteinizing Hormone - pharmacology; Meiosis; Meiosis - drug effects; Mice; Mouse ovarian follicle; natriuretic peptide receptors; Natriuretic Peptide, C-Type - metabolism; Natriuretic Peptide, C-Type - pharmacology; natriuretic peptides; Oocyte; Oocytes; Oocytes - cytology; Oocytes - metabolism; Ovarian Follicle - cytology; Ovarian Follicle - enzymology; Prophase; Receptors, Atrial Natriuretic Factor - antagonists & inhibitors; Receptors, Atrial Natriuretic Factor - metabolism; Luteinizing hormone; Meiosis; Guanylyl cyclase; Cyclic GMP; Oocyte; Mouse ovarian follicle
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2012.04.019

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 20min, 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 2h, 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. ► Cyclic GMP from granulosa cells maintains mouse oocytes in meiotic arrest. ► NPR2 is the primary guanylyl cyclase in granulosa cells. ► Luteinizing hormone treatment decreases NPR2 activity to 50% by 20min. ► LH treatment also decreases the NPR2 agonist, CNP, but only after 2h. ► These LH actions reduce granulosa and oocyte cGMP, causing meiotic resumption.