Luteinizing hormone causes MAP kinase-dependent phosphorylation and closure of connexin 43 gap junctions in mouse ovarian follicles: one of two paths to meiotic resumption

Development. 2008 Oct;135(19):3229-38. doi: 10.1242/dev.025494.


Luteinizing hormone (LH) acts on ovarian follicles to reinitiate meiosis in prophase-arrested mammalian oocytes, and this has been proposed to occur by interruption of a meioisis-inhibitory signal that is transmitted through gap junctions into the oocyte from the somatic cells that surround it. To investigate this idea, we microinjected fluorescent tracers into live antral follicle-enclosed mouse oocytes, and we demonstrate for the first time that LH causes a decrease in the gap junction permeability between the somatic cells, prior to nuclear envelope breakdown (NEBD). The decreased permeability results from the MAP kinase-dependent phosphorylation of connexin 43 on serines 255, 262 and 279/282. We then tested whether the inhibition of gap junction communication was sufficient and necessary for the reinitiation of meiosis. Inhibitors that reduced gap junction permeability caused NEBD, but an inhibitor of MAP kinase activation that blocked gap junction closure in response to LH did not prevent NEBD. Thus, both MAP kinase-dependent gap junction closure and another redundant pathway function in parallel to ensure that meiosis resumes in response to LH.

Publication types

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

MeSH terms

  • Animals
  • Cell Membrane Permeability / drug effects
  • Connexin 43 / chemistry
  • Connexin 43 / metabolism*
  • Cumulus Cells / cytology
  • Cumulus Cells / drug effects
  • Cumulus Cells / metabolism
  • Female
  • Gap Junctions / drug effects*
  • Gap Junctions / metabolism
  • Granulosa Cells / cytology
  • Granulosa Cells / drug effects
  • Granulosa Cells / metabolism
  • Luteinizing Hormone / pharmacology*
  • Meiosis / drug effects*
  • Meiosis / physiology
  • Mice
  • Mitogen-Activated Protein Kinase Kinases / metabolism*
  • Oocytes / cytology
  • Oocytes / drug effects
  • Oocytes / metabolism
  • Ovarian Follicle / cytology
  • Ovarian Follicle / drug effects*
  • Ovarian Follicle / metabolism*
  • Phosphorylation
  • Serine / chemistry
  • Tissue Culture Techniques


  • Connexin 43
  • Serine
  • Luteinizing Hormone
  • Mitogen-Activated Protein Kinase Kinases