Dependence of fertility on kisspeptin–Gpr54 signaling at the GnRH neuron
Milen Kirilov,
Jenny Clarkson,
Xinhuai Liu,
Juan Roa,
Pauline Campos,
Rob Porteous,
Günther Schütz and
Allan E. Herbison ()
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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
Nature Communications, 2013, vol. 4, issue 1, 1-11
Abstract:
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.
Date: 2013
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3492
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DOI: 10.1038/ncomms3492
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