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FGF21 contributes to neuroendocrine control of female reproduction.

ABSTRACT: Preventing reproduction during nutritional deprivation is an adaptive process that is conserved and essential for the survival of species. In mammals, the mechanisms that inhibit fertility during starvation are complex and incompletely understood. Here we show that exposure of female mice to fibroblast growth factor 21 (FGF21), a fasting-induced hepatokine, mimics infertility secondary to starvation. Mechanistically, FGF21 acts on the suprachiasmatic nucleus (SCN) in the hypothalamus to suppress the vasopressin-kisspeptin signaling cascade, thereby inhibiting the proestrus surge in luteinizing hormone. Mice lacking the FGF21 co-receptor, ?-Klotho, in the SCN are refractory to the inhibitory effect of FGF21 on female fertility. Thus, FGF21 defines an important liver-neuroendocrine axis that modulates female reproduction in response to nutritional challenge.

SUBMITTER: Owen BM

PROVIDER: S-EPMC3769455 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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FGF21 contributes to neuroendocrine control of female reproduction.

Owen Bryn M BM Bookout Angie L AL Ding Xunshan X Lin Vicky Y VY Atkin Stan D SD Gautron Laurent L Kliewer Steven A SA Mangelsdorf David J DJ

Nature medicine 20130811 9

Preventing reproduction during nutritional deprivation is an adaptive process that is conserved and essential for the survival of species. In mammals, the mechanisms that inhibit fertility during starvation are complex and incompletely understood. Here we show that exposure of female mice to fibroblast growth factor 21 (FGF21), a fasting-induced hepatokine, mimics infertility secondary to starvation. Mechanistically, FGF21 acts on the suprachiasmatic nucleus (SCN) in the hypothalamus to suppress ...[more]

PMID: 23933983

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