Dependence of fertility on kisspeptin-Gpr54 signaling at the GnRH neuron.
Nat Commun
; 4: 2492, 2013.
Article
em En
| MEDLINE
| ID: mdl-24051579
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 Gpr54â»/â» 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Hormônio Liberador de Gonadotropina
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Receptores Acoplados a Proteínas G
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Kisspeptinas
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Hipotálamo
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Infertilidade
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Neurônios
Limite:
Animals
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article