Mechanism of growth hormone insensitivity induced by endotoxin

Abstract

Aim: 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.

Conclusion: 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.