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

Dev Biol. 2012 Jun 15;366(2):308-16. doi: 10.1016/j.ydbio.2012.04.019. Epub 2012 Apr 21.


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 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclic GMP / metabolism
  • Female
  • Granulosa Cells / metabolism
  • Luteinizing Hormone / metabolism*
  • Luteinizing Hormone / pharmacology
  • Meiosis / drug effects
  • Mice
  • Natriuretic Peptide, C-Type / metabolism
  • Natriuretic Peptide, C-Type / pharmacology
  • Oocytes / cytology
  • Oocytes / metabolism*
  • Ovarian Follicle / cytology
  • Ovarian Follicle / enzymology*
  • Receptors, Atrial Natriuretic Factor / antagonists & inhibitors
  • Receptors, Atrial Natriuretic Factor / metabolism*


  • Natriuretic Peptide, C-Type
  • Luteinizing Hormone
  • Receptors, Atrial Natriuretic Factor
  • atrial natriuretic factor receptor B
  • Cyclic GMP