FGF21 contributes to neuroendocrine control of female reproduction

Bryn M. Owen, Angie L. Bookout, Xunshan Ding, Vicky Y. Lin, Stan D. Atkin, Laurent Gautron, Steven A. Kliewer, David J. Mangelsdorf

Research output: Contribution to journalArticlepeer-review

166 Scopus citations


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, β-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.

Original languageEnglish (US)
Pages (from-to)1153-1156
Number of pages4
JournalNature medicine
Issue number9
StatePublished - Sep 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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