AIM:Critical illnesses such as sepsis,trauma,and burnscause a growth hormone insensitivity,which leads to anincreased negative nitrogen balance.Endotoxin isgenerously released into blood under these conditions andstimulates the production of proinflammatory cytokines suchas TNF-α,IL-6,and IL-1,which may play a very importantrole in inducing the growth hormone insensitivity.Theobjective of this current study was to investigate the role ofendotoxin,TNF-α and IL-6 in inducing the growth hormoneinsensitivity at the receptor and post-receptor levels.METHODS:Spague-Dawley rats were injected withendotoxin,TNF-α,and IL-6,respectively and part of ratsinjected with endotoxin was treated with exogenoussomatotropin simultaneously.All rats were killed at differenttime points.The expression of IGF-I,GHR,SOCS-3 and β-actin mRNA in the liver was detected by RT-PCR and the GHlevels were measured by radioimmunoassay,the levels ofTNF-α and IL-6 were detected by ELISA.RESULTS:There was no significant difference in serous GHlevels between experimental group and control rats afterendotoxin injection,however,liver IGF-I mRNA expressionhad been obviously down-regulated in endotoxemic rats.Liver GHR mRNA expression also had a predominant down-regulation after endotoxin injection.The lowest regulation ofliver IGF-I mRNA expression occurred at 12 h after LPSinjection,being decreased by 53% compared with controlrats.For GHR mRNA expression,the lowest expressionoccurred at 8 h and had a 81% decrease.Although SOCS-3mRNA was weakly expressed in control rats.it was stronglyup-regulated after LPS injection and had a 7.84 timesincrease compared with control rats.Exogenous GH couldenhance IGF-I mRNA expression in control rats,but it didfail to prevent the decline in IGF-I mRNA expression inendotoxemic rats.Endotoxin stimulated the production ofTNF-α and IL-6,and the elevated IL-6 levels was shown apositive correlation with increased SOCS-3 mRNAexpression.The liver GHR mRNA expression was obviouslydown-regulated after TNF-α iv injection and had a 40%decrease at 8 h,but the liver SOCS-3 mRNA expression wasthe 4.94 times up-regulation occurred at 40 min after IL-6injection.CONCLUSION:The growth hormone insensitivity could beinduced by LPS injection,which was associated with down- regulated GHR mRNA expression at receptor level and withup-regulated SOCS-3 mRNA expression at post-receptorlevel.The in vivo biological activities of LPS were mediatedby TNF-α and IL-6 indirectly,and TNF-α and IL-6 may exerttheir effects on.the receptor and post-receptor levelsrespectively.
