The decrease in hepatic IGF-I gene expression in arthritic rats is not associated with modifications in hepatic GH receptor mRNA

Department of Physiology, Faculty of Medicine, Complutense University, 28040 Madrid, Spain. ALC@eucmax.sim.ucm.es

OBJECTIVE: Adjuvant-induced arthritis induces a catabolic response, and a decrease in circulating IGF-I. Hypermetabolism and GH insensitivity have been described in acute inflammation. The aim of this study was to analyze whether impaired IGF-I secretion in arthritic rats can be attributed to hepatic GH resistance. DESIGN AND METHODS: Male Wistar rats were injected with complete Freund's adjuvant, and 14 days afterwards arthritic and control rats were injected daily with recombinant human GH (rhGH) (3 IU/kg) or saline for 8 days. GH receptor (GHR) gene expression in the liver and the effect of rhGH on hepatic IGF-I synthesis in arthritic rats were examined. RESULTS: There was a significant decrease in hepatic concentrations of IGF-I (P < 0.01) as well as in the IGF-I gene expression in arthritic but not in pair-fed rats. In contrast, arthritis did not modify GHR mRNA levels in the liver. The 8 day administration of rhGH resulted in an increase in body weight gain in arthritic but not in control rats. There was an increase in hepatic IGF-I synthesis and in GHR mRNA levels after rhGH treatment, both in control and in arthritic rats. Two endotoxin lipopolysaccharide (LPS) (1 mg/kg) injections decreased hepatic concentrations of IGF-I and IGF-I mRNA (P < 0.01). Contrary to the results obtained in arthritic rats, mRNA expression of GHR in the liver was lower in LPS- than in saline-treated rats (P < 0.01). CONCLUSION: These data suggest that the decrease in IGF-I synthesis induced by chronic arthritis is not secondary to GH resistance.

This article has been cited by other articles:

				M. Granado, A. I Martin, M{a} A. Villanua, and A. Lopez-Calderon Experimental arthritis inhibits the insulin-like growth factor-I axis and induces muscle wasting through cyclooxygenase-2 activation Am J Physiol Endocrinol Metab, June 1, 2007; 292(6): E1656 - E1665. [Abstract] [Full Text] [PDF]

				M. Granado, T. Priego, A. I. Martin, M{a} A. Villanua, and A. Lopez-Calderon Ghrelin receptor agonist GHRP-2 prevents arthritis-induced increase in E3 ubiquitin-ligating enzymes MuRF1 and MAFbx gene expression in skeletal muscle Am J Physiol Endocrinol Metab, December 1, 2005; 289(6): E1007 - E1014. [Abstract] [Full Text] [PDF]

				T. Priego, I. Ibanez de Caceres, A. I. Martin, M. A. Villanua, and A. Lopez-Calderon NO plays a role in LPS-induced decreases in circulating IGF-I and IGFBP-3 and their gene expression in the liver Am J Physiol Endocrinol Metab, January 1, 2004; 286(1): E50 - E56. [Abstract] [Full Text] [PDF]