Inhibition of Growth Hormone Signaling by the Fasting-Induced Hormone FGF21

Takeshi Inagaki, Vicky Y. Lin, Regina Goetz, Moosa Mohammadi, David J. Mangelsdorf, Steven A. Kliewer

Research output: Contribution to journalArticle

256 Scopus citations

Abstract

Starvation blocks the actions of growth hormone (GH) and inhibits growth through mechanisms that are not well understood. In this report, we demonstrate that fibroblast growth factor 21 (FGF21), a hormone induced by fasting, causes GH resistance. In liver, FGF21 reduces concentrations of the active form of signal transducer and activator of transcription 5 (STAT5), a major mediator of GH actions, and causes corresponding decreases in the expression of its target genes, including insulin-like growth factor 1 (IGF-1). FGF21 also induces hepatic expression of IGF-1 binding protein 1 and suppressor of cytokine signaling 2, which blunt GH signaling. Chronic exposure to FGF21 markedly inhibits growth in mice. These data suggest a central role for FGF21 in inhibiting growth as part of its broader role in inducing the adaptive response to starvation.

Original languageEnglish (US)
Pages (from-to)77-83
Number of pages7
JournalCell Metabolism
Volume8
Issue number1
DOIs
StatePublished - Jul 2 2008

Keywords

  • HUMDISEASE
  • SIGNALING

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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