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

Author

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  • Milen Kirilov

    (Molecular Biology of the Cell I, German Cancer Research Center, Im Neuenheimer Feld 280)

  • Jenny Clarkson

    (Centre for Neuroendocrinology, University of Otago School of Medical Sciences)

  • Xinhuai Liu

    (Centre for Neuroendocrinology, University of Otago School of Medical Sciences)

  • Juan Roa

    (Centre for Neuroendocrinology, University of Otago School of Medical Sciences)

  • Pauline Campos

    (Centre for Neuroendocrinology, University of Otago School of Medical Sciences)

  • Rob Porteous

    (Centre for Neuroendocrinology, University of Otago School of Medical Sciences)

  • Günther Schütz

    (Molecular Biology of the Cell I, German Cancer Research Center, Im Neuenheimer Feld 280)

  • Allan E. Herbison

    (Centre for Neuroendocrinology, University of Otago School of Medical Sciences)

Abstract

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.

Suggested Citation

  • Milen Kirilov & Jenny Clarkson & Xinhuai Liu & Juan Roa & Pauline Campos & Rob Porteous & Günther Schütz & Allan E. Herbison, 2013. "Dependence of fertility on kisspeptin–Gpr54 signaling at the GnRH neuron," Nature Communications, Nature, vol. 4(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3492
    DOI: 10.1038/ncomms3492
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