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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.

SUBMITTER: Inagaki T

PROVIDER: S-EPMC2575072 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature

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

Inagaki Takeshi T Lin Vicky Y VY Goetz Regina R Mohammadi Moosa M Mangelsdorf David J DJ Kliewer Steven A SA

Cell metabolism 20080701 1

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 gro ...[more]

PMID: 18585098

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