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Dependence of fertility on kisspeptin-Gpr54 signaling at the GnRH neuron

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...

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Hauptverfasser: Kirilov, Milen (VerfasserIn) , Clarkson, Jenny (VerfasserIn) , Liu, Xinhuai (VerfasserIn) , Roa, Juan (VerfasserIn) , Campos, Pauline (VerfasserIn) , Porteous, Rob (VerfasserIn) , Schütz, Günther (VerfasserIn) , Herbison, Allan E. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 20 Sep 2013
In: Nature Communications
Year: 2013, Jahrgang: 4, Pages: 1-11
ISSN:2041-1723
DOI:10.1038/ncomms3492
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/ncomms3492
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/ncomms3492
Volltext
Verfasserangaben:Milen Kirilov, Jenny Clarkson, Xinhuai Liu, Juan Roa, Pauline Campos, Rob Porteous, Günther Schütz & Allan E. Herbison
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 22.06.2022
Beschreibung:Online Resource
ISSN:2041-1723
DOI:10.1038/ncomms3492

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