First Author | Kirilov M | Year | 2013 |
Journal | Nat Commun | Volume | 4 |
Pages | 2492 | PubMed ID | 24051579 |
Mgi Jnum | J:206044 | Mgi Id | MGI:5547688 |
Doi | 10.1038/ncomms3492 | Citation | Kirilov M, et al. (2013) Dependence of fertility on kisspeptin-Gpr54 signaling at the GnRH neuron. Nat Commun 4:2492 |
abstractText | Signaling between kisspeptin and its receptor, G-protein-coupled receptor 54 (Gpr54), is now recognized as being essential for normal fertility. However, the key cellular location of kisspeptin-Gpr54 signaling is unknown. Here we create a mouse with a GnRH neuron-specific deletion of Gpr54 to assess the role of gonadotropin-releasing hormone (GnRH) neurons. Mutant mice are infertile, fail to go through puberty and exhibit markedly reduced gonadal size and follicle-stimulating hormone levels alongside GnRH neurons that are unresponsive to kisspeptin. In an attempt to rescue the infertile phenotype of global Gpr54(-)/(-) mutants, we use BAC transgenesis to target Gpr54 to the GnRH neurons. This results in mice with normal puberty onset, estrous cyclicity, fecundity and a recovery of kisspeptin's stimulatory action upon GnRH neurons. Using complimentary cell-specific knockout and knockin approaches we demonstrate here that the GnRH neuron is the key site of kisspeptin-Gpr54 signaling for fertility. |