Inhibition of growth hormone signaling by the fasting-induced hormone FGF21 (Cell Metabolism, 2008, 8:77--83)

報告日期: 2008/10/28
報告時間: 16:00/16:50
報告學生: 王佩文
講評老師: 王育民
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/971028-2.pdf

Inhibition of Growth Hormone Signaling by the Fasting-Induced Hormone FGF21

Takeshi Inagaki, Vicky Y. Lin, Regina Goetz, Moosa Mohammadi, David J. Mangelsdorf, and Steven A. Kliewer

Cell Metab. 2008 Jul;8(1):77-83.

 

Speacker: 王佩文

Commentator: 王育民 教授

Date: 2008/10/28

Place: Room 602

 

ABSTRACT

Starvation could decrease hepatic mRNA level and circulating concentration of insulin-like growth factor 1 (IGF-1) and acid-labile subunit (ALS) and induce IGF-1 binding protein 1 (IGFBP-1) expression to block the actions of growth hormone (GH) and inhibits growth but the mechanisms that are not well understood. A recent study showed that fasted rats have reduced hepatic phosphorylation of signal transducer and activator of transcription 5 (STAT5) in response to injected GH, suggesting that fasting might inhibit transcription of the IGF-1 and ALS genes by reducing STAT5 activity. In this report, we demonstrate that fibroblast growth factor 21 (FGF21), a hormone induced by fasting, causes GH resistance. FGF21 is a member of a subfamily of FGFs and most similar to FGF19 (~35% amino acid identity). The subfamily is also including FGF15 and FGF23 and function as endocrine hormones. The expression of FGF21 was most abundantly expressed in the liver and pancreas and had a main function to regulate metabolism. FGF21 could response to fasting and regulate metabolism to establish it as a major endocrine regulator. In liver, FGF21 reduces concentrations of the active form of STAT5, a major mediator of GH actions, and causes corresponding decreases in the expression of its target genes, including 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.

 

REFERENCE

Takeshi Inagaki et al., Endocrine regulation of the fasting response by PPARalpha-mediated induction of fibroblast growth factor 21. Cell Metab. 2007 Jun;5(6):415-25.

Herrington J. et al., The role of STAT proteins in growth hormone signaling. Oncogene. 2000 May 15;19(21):2585-97. Review.