title: Persistent cAMP Signaling by Internalized LH Receptors in Ovarian Follicles.
abstract: 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.
authors.affiliation: Institute of Pharmacology and Toxicology, University of Würzburg, and Rudolf Virchow Center, Bio-Imaging Center, 97078 Würzburg, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Lyga
authors.affiliation: Institute of Pharmacology and Toxicology, University of Würzburg, and Rudolf Virchow Center, Bio-Imaging Center, 97078 Würzburg, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Volpe
authors.affiliation: Institute of Pharmacology and Toxicology, University of Würzburg, and Rudolf Virchow Center, Bio-Imaging Center, 97078 Würzburg, Germany.
authors.forename: Ruth C
authors.initials: RC
authors.lastname: Werthmann
authors.affiliation: Institute of Pharmacology and Toxicology, University of Würzburg, and Rudolf Virchow Center, Bio-Imaging Center, 97078 Würzburg, Germany.
authors.forename: Konrad
authors.initials: K
authors.lastname: Götz
authors.affiliation: Institute of Pharmacology and Toxicology, University of Würzburg, and Rudolf Virchow Center, Bio-Imaging Center, 97078 Würzburg, Germany.
authors.forename: Titiwat
authors.initials: T
authors.lastname: Sungkaworn
authors.affiliation: Institute of Pharmacology and Toxicology, University of Würzburg, and Rudolf Virchow Center, Bio-Imaging Center, 97078 Würzburg, Germany.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Lohse
authors.affiliation: Institute of Pharmacology and Toxicology, University of Würzburg, and Rudolf Virchow Center, Bio-Imaging Center, 97078 Würzburg, Germany.
authors.forename: Davide
authors.initials: D
authors.lastname: Calebiro
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology; D005260:Female; D031541:Fluorescence Resonance Energy Transfer; D007986:Luteinizing Hormone / Q000494:pharmacology; D008540:Meiosis / Q000187:drug effects; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D006080:Ovarian Follicle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011974:Receptors, LH / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D011974:Receptors, LH; D007986:Luteinizing Hormone; D000242:Cyclic AMP