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

Inhibition of growth hormone signaling by the fasting-induced hormone FGF21.
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DOI:
10.1016/j.cmet.2008.05.006
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发表时间:
2008-07
期刊:
影响因子:
29
通讯作者:
Kliewer, Steven A.
Kliewer, Steven A.
中科院分区:
生物学1区
文献类型:
--
作者:
Inagaki, Takeshi;Lin, Vicky Y.;Goetz, Regina;Mohammadi, Moosa;Mangelsdorf, David J.;Kliewer, Steven A.

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饥饿阻断生长激素(GH)的作用并通过尚不清楚的机制抑制生长。在本报告中,我们证明了成纤维细胞生长因子21 (FGF21),一种由禁食诱导的激素,引起生长激素抵抗。在肝脏中,FGF21降低了信号换能器和转录激活因子5 (STAT5)的活性形式的浓度,STAT5是生长激素作用的主要介质,并导致其靶基因包括胰岛素样生长因子1 (IGF-1)的表达相应降低。FGF21还诱导肝脏表达IGF-1结合蛋白1和细胞因子信号传导抑制因子2,从而减弱GH信号传导。长期暴露于FGF21显著抑制小鼠生长。这些数据表明,FGF21在抑制生长方面发挥着核心作用,这是其在诱导对饥饿的适应性反应方面发挥的更广泛作用的一部分。
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.
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