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Cell Metab. 2008 Jul;8(1):77-83. doi: 10.1016/j.cmet.2008.05.006.

Inhibition of growth hormone signaling by the fasting-induced hormone FGF21.

Author information

1
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

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.

PMID:
18585098
PMCID:
PMC2575072
DOI:
10.1016/j.cmet.2008.05.006
[Indexed for MEDLINE]
Free PMC Article

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