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

被引：351

作者：

Inagaki, Takeshi ^{[1
]}

Lin, Vicky Y. ^{[2
,3
]}

Goetz, Regina ^{[4
]}

Mohammadi, Moosa ^{[4
]}

Mangelsdorf, David J. ^{[2
,3
]}

Kliewer, Steven A. ^{[1
,2
]}

机构：

[1] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA

[2] Univ Texas SW Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA

[3] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA

[4] NYU, Sch Med, Dept Pharmacol, New York, NY 10016 USA

来源：

CELL METABOLISM | 2008年 / 8卷 / 01期

关键词：

D O I：

10.1016/j.cmet.2008.05.006

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：77 / 83

页数：7

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