Search
Check Out Our Sponsors
Latest topics
Endotoxin attenuates growth hormone-induced hepatic insulin-like growth factor I expression by inhibiting JAK2/STAT5 signal transduction and STAT5b DNA binding
Page 1 of 1
Endotoxin attenuates growth hormone-induced hepatic insulin-like growth factor I expression by inhibiting JAK2/STAT5 signal transduction and STAT5b DNA binding
Endotoxin attenuates growth hormone-induced hepatic insulin-like growth factor I expression by inhibiting JAK2/STAT5 signal transduction and STAT5b DNA binding
Yu Chen,1 Difei Sun,1 Vidya M. R. Krishnamurthy,2 and Ralph Rabkin1,2
1Department Medicine, Stanford University, Stanford; and 2Research Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, California
Submitted 1 November 2006 ; accepted in final form 19 February 2007
ABSTRACT
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 insulin-like growth factor-I (IGF-I) 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-I expression, there might also be a more distal defect. Conscious rats were given endotoxin and studied 4 h 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 tumor necrosis factor-α and interleukin-6 mRNA expression accompanied by elevated levels of inhibitors of GH signaling, namely cytokine-inducible suppressors of cytokine signaling-1 and -3 and cytokine-inducible SH2 protein (CIS). Nuclear phosphorylated STAT5b levels were significantly depressed to 61% of the control values and represent a potential cause of the reduced GH-induced IGF-I expression. In addition, binding of phosphorylated 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-I gene transcription. Interestingly, when endotoxin-treated rats were treated with GH, there was a marked increase in proinflammatory cytokine gene expression in the liver. 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.
_________________
"Mass paranoia is a mode, not a melody" - Greg Graffin
"When you're going through hell, keep going!" - Winstone Churchill
a<r- Admin
- Posts : 819
Join date : 2011-05-12
Age : 33
Similar topics
» Sex hormone-binding globulin mediates steroid hormone signal transduction at the plasma membrane
» Dihydrotestosterone inhibits hair growth in mice by inhibiting insulin-like growth factor-I production in dermal papillae
» Inhibition of GSK-3 enhances the expression of alkaline phosphatase and insulin-like growth factor-1
» The expression of insulin-like growth factor 1 in follicular dermal papillae correlates with therapeutic efficacy of finasteride in androgenetic alopecia
» Function of Insulin - Insulin Suppresses Endotoxin-Induced Oxidative, Nitrosative, and Inflammatory Stress in Humans
» Dihydrotestosterone inhibits hair growth in mice by inhibiting insulin-like growth factor-I production in dermal papillae
» Inhibition of GSK-3 enhances the expression of alkaline phosphatase and insulin-like growth factor-1
» The expression of insulin-like growth factor 1 in follicular dermal papillae correlates with therapeutic efficacy of finasteride in androgenetic alopecia
» Function of Insulin - Insulin Suppresses Endotoxin-Induced Oxidative, Nitrosative, and Inflammatory Stress in Humans
Page 1 of 1
Permissions in this forum:
You cannot reply to topics in this forum
Sat Apr 27, 2024 4:00 pm by CausticSymmetry
» *The first scientific evidence in 2021 that viruses do not exist*
Fri Apr 26, 2024 12:44 pm by CausticSymmetry
» Potential Natural Products Regulation of Molecular Signaling Pathway in Dermal Papilla Stem Cells
Wed Apr 17, 2024 7:44 am by CausticSymmetry
» Breast Biopsy
Sun Apr 14, 2024 2:23 am by shaftless
» Sorry if brought up before but: Best topical to help aid in breaking up fibrosis?
Sat Apr 13, 2024 2:51 am by Hoppipolla
» solar eclipse on april 8
Thu Apr 11, 2024 4:04 am by shaftless
» Role and Mechanisms of Phytochemicals in Hair Growth and Health
Wed Apr 10, 2024 4:20 am by CausticSymmetry
» IH Regimen
Tue Apr 09, 2024 4:25 pm by CF
» Exosome Theory and Herpes
Mon Apr 08, 2024 11:16 am by MikeGore