Growth hormone insensitivity of rats under the endotoxemic condition.
- Author:
Ping WANG
1
;
Ning LI
;
Jieshou LI
;
Weiqin LI
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Down-Regulation; Growth Hormone; metabolism; pharmacology; Insulin-Like Growth Factor I; genetics; metabolism; Interleukin-6; pharmacology; physiology; Lipopolysaccharides; toxicity; Liver; drug effects; metabolism; Male; RNA, Messenger; metabolism; Rats; Rats, Sprague-Dawley; Receptors, Somatotropin; genetics; Suppressor of Cytokine Signaling Proteins; genetics; metabolism; Tumor Necrosis Factor-alpha; pharmacology; physiology
- From: Chinese Journal of Surgery 2002;40(12):940-944
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the mechanism of growth hormone insensitivity of rats under the endotoxemic condition.
METHODSSprague Dawley rats (n = 180) were injected endotoxin, TNF-alpha, and IL-6 respectively. Part of endotoxin injected rats were treated with exogenous somatotropin simultaneously, and all rats were killed at different time points. Liver expression of IGF I, GHR and SOCS-3 mRNA was detected by RT-PCR, the levels of growth hormone (GH) were measured by radioimmunoassay, and the levels of TNF-alpha and IL-6 were detected by ELISA.
RESULTSSerum GH levels showed no significant change after endotoxin injection; however, liver IGF I and GHR mRNA expressions were obviously down-regulated in endotoxemic rats, with the lowest decrease of 53% and 89% respectively. Although SOCS-3 mRNA was weakly expressed in control rats, it was strongly up-regulated in endotoxemic rats and the marked increase was 7.84 folds. The higher LPS dosage induced marked GHR mRNA down-regulation and marked SOCS-3 mRNA up-regulation. Exogenous GH made IGFI mRNA expression increase 25% in the control rats, but it did fail to prevent the decline in IGFI mRNA expression in endotoxemic rats. Endotoxin 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. Liver GHR mRNA expression was obviously down-regulated after TNF-alpha i.v. injection, but for IL-6, it mainly up-regulated the liver SOCS-3 mRNA expression.
CONCLUSIONThe growth hormone insensitivity could be induced by LPS injection, which might be associated with down-regulated GHR mRNA expression and up-regulated SOCS-3 mRNA expression. The in vivo biological activities of LPS may be partially mediated by TNF-alpha and IL-6 at different aspects.
