Persistent cAMP signaling by internalized LH receptors in ovarian follicles

Sandra Lyga, Silvia Volpe, Ruth C. Werthmann, Konrad Götz, Titiwat Sungkaworn, Martin J. Lohse, Davide Calebiro*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)


A crucial event in female reproduction occurs at midcycle, when a LH peak induces the final maturation of ovarian follicles. LH signals via a G protein-coupled receptor selectively expressed in the outermost follicular cell layers. However, how LH signals are relayed inside these cells and finally to the oocyte is incompletely understood. Here, we monitored LH signaling in intact ovarian follicles of transgenic mice expressing a fluorescent cAMP sensor. We found that LH stimulation induces 2 phases of cAMP signaling in all cell layers surrounding the oocyte. Interfering with LH receptor internalization abolished the second, persistent cAMP phase and partially inhibited oocyte meiosis resumption. These data suggest that persistent cAMP signals from internalized LH receptors contribute to transmitting LH effects inside follicle cells and ultimately to the oocyte. Thus, this study indicates that the recently proposed paradigm of cAMP signaling by internalized G protein-coupled receptors is implicated in receptor function and is physiologically relevant.

Original languageEnglish
Pages (from-to)1613-1621
Number of pages9
Issue number4
Publication statusPublished - 1 Apr 2016

ASJC Scopus subject areas

  • Endocrinology


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