title: Mechanism of growth hormone insensitivity induced by endotoxin.
abstract: OBJECTIVE
  To investigate the mechanism of growth hormone (GH) insensitivity induced by endotoxin at receptor and post-receptor levels.
  
  
  METHODS
  Sprague-Dawley rats were injected endotoxin along with or without GH administration. The liver expression of insulin-like growth factor I (IGF-I), GH receptor (GHR), and suppresor of cytokine signaling (SOCS)-3 mRNA were detected by reverse transcriptase polymerase cha in reaction, the GH levels were measured by radioimmunoassay, the levels of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) were detected by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Serum GH levels had no significant difference compared with control rats after endotoxin injection, however, liver IGF-I mRNA expression was obviously down-regulated in endotoxemic rats. Liver GHR mRNA expression was predominantly down-regulated after LPS injection; although SOCS-3 mRNA was weakly expressed in control rats, it was strongly up-regulated in endotoxemic rats. Endotoxine stimulated the production of TNF-alpha and IL-6, and the elevated IL-6 levels showed a positive correlation with increased SOCS-3 mRNA expression. Exogenous GH could enhance IGF-I mRNA expression in control rats, but it did fail to prevent the decline in IGF-I mRNA expression in endotoxemic rats. Two different LPS dosages (7.5 mg/kg and 5.0 mg/kg) produced the same down-regulation of IGF-I mRNA expression, however, the higher LPS dosage induced more GHR mRNA down-regulation and more SOCS-3 mRNA up-regulation.
  
  
  CONCLUSIONS
  The mechanism of growth hormone insensitivity induced by endotoxin was associated with down-regulated GHR mRNA expression at receptor level and up-regulated SOCS-3 mRNA expression at post-receptor level. The inhibition at post-receptor level had close relationship with the increased IL-6 secretion.
authors.affiliation: Medical College of Nanjing University, Reseach Institute of General Surgery, Jinling Hospital, Nanjing 210002, China. wpmd@yahoo.com
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Jie-Shou
authors.initials: JS
authors.lastname: Li
mesh_terms: D000818:Animals; D004926:Escherichia coli; D013006:Growth Hormone / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008297:Male; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011986:Receptors, Somatotropin / Q000378:metabolism*; D012097:Repressor Proteins; D012680:Sensitivity and Specificity; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D011506:Proteins; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D012097:Repressor Proteins; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone