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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological
  • Animals
  • Fasting / metabolism
  • Fibroblast Growth Factors / physiology*
  • Growth
  • Growth Hormone / antagonists & inhibitors*
  • Growth Hormone / physiology
  • Liver / metabolism
  • Mice
  • STAT5 Transcription Factor / antagonists & inhibitors*
  • Signal Transduction
  • Starvation / metabolism


  • STAT5 Transcription Factor
  • fibroblast growth factor 21
  • Fibroblast Growth Factors
  • Growth Hormone