title: Inhibition of growth hormone signaling by the fasting-induced hormone FGF21.
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.
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Inagaki
authors.forename: Vicky Y
authors.initials: VY
authors.lastname: Lin
authors.forename: Regina
authors.initials: R
authors.lastname: Goetz
authors.forename: Moosa
authors.initials: M
authors.lastname: Mohammadi
authors.forename: David J
authors.initials: DJ
authors.lastname: Mangelsdorf
authors.forename: Steven A
authors.initials: SA
authors.lastname: Kliewer
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D005215:Fasting / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000502:physiology*; D006128:Growth; D013006:Growth Hormone / Q000037:antagonists & inhibitors* / Q000502:physiology; D008099:Liver / Q000378:metabolism; D051379:Mice; D050799:STAT5 Transcription Factor / Q000037:antagonists & inhibitors*; D015398:Signal Transduction; D013217:Starvation / Q000378:metabolism
chemical_list: D050799:STAT5 Transcription Factor; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D013006:Growth Hormone