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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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Main Authors: Kirilov, Milen (Author) , Clarkson, Jenny (Author) , Liu, Xinhuai (Author) , Roa, Juan (Author) , Campos, Pauline (Author) , Porteous, Rob (Author) , Schütz, Günther (Author) , Herbison, Allan E. (Author)
Format: Article (Journal)
Language:English
Published: 20 Sep 2013
In: Nature Communications
Year: 2013, Volume: 4, Pages: 1-11
ISSN:2041-1723
DOI:10.1038/ncomms3492
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/ncomms3492
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/ncomms3492
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Author Notes:Milen Kirilov, Jenny Clarkson, Xinhuai Liu, Juan Roa, Pauline Campos, Rob Porteous, Günther Schütz & Allan E. Herbison
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Summary: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.
Item Description:Gesehen am 22.06.2022
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/ncomms3492

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