Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

ENDOTOXIN ATTENUATES GROWTH HORMONE INDUCED HEPATIC INSULIN-LIKE GROWTH FACTOR-1 EXPRESSION BY INHIBITING JAK2/STAT5 SIGNAL TRANSDUCTION AND STAT5b DNA BINDING.

Authors: Chen, Y  Sun, D  Krishnamurthy, VM  Rabkin, R 
Citation: Chen Y, etal., Am J Physiol Endocrinol Metab. 2007 Feb 27;.
Pubmed: (View Article at PubMed) PMID:17327369
DOI: Full-text: DOI:10.1152/ajpendo.00581.2006

Gram negative sepsis with release of endotoxin is a frequent cause of cachexia that develops partly because of resistance to growth hormone (GH) with reduced IGF-1 expression. We set out to more fully characterize the mechanisms for the resistance and to determine whether in addition to a defect in the janus kinase 2 (JAK2)-signal transducer and activator of transcription (STAT) 5b pathway, required for GH induced IGF-1 expression, there might also be a more distal defect. Conscious rats were given endotoxin and studied four hours later. In liver of these animals, GH induced JAK2 and STAT5 phosphorylation was impaired and appeared to be caused, at least in part, by a marked increase in hepatic TNFα and IL-6 mRNA expression accompanied by elevated levels of inhibitors of GH signaling, namely cytokine inducible suppressors of cytokine signaling -1, -3 and CIS. Nuclear phosphorylated STAT5b levels were significantly depressed to 61% of the control values, and represents a potential cause of the reduced GH induced IGF-1 expression. In addition, binding of the activated STAT5b to DNA was reduced to an even greater extent and averaged 17% of the normal control value. This provides a further explanation for the impaired IGF-1 gene transcription. Interestingly when endotoxin treated rats were treated with GH, there was a marked increase in pro-inflammatory cytokine gene expression in the liver and if such a response were to occur in humans, this might provide a partial explanation for the adverse effect of GH treatment reported in critically ill patients Key words: lipopolysaccharide, cytokines, inflammation.

Annotation

Disease Annotations
Gene Ontology Annotations
Objects Annotated

Additional Information

 
RGD Object Information
RGD ID: 1601383
Created: 2007-04-18
Species: All species
Last Modified: 2007-04-18
Status: ACTIVE



NHLBI Logo

RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.