DIFFERENTIAL ROLE OF GLUCOCORTICOIDS IN MEDIATING ENDOTOXIN-INDUCED CHANGES IN IGF-I AND IGFBP-1

The purpose of the present study was to determine whether endogenous e levations in glucocorticoids mediate the changes in insulin-like growt h factor (IGF) I and IGF binding protein (IGFBP) 1 levels in plasma an d tissues observed after in vivo administration of lipopolysaccharide (LPS). In overnight-fasted male rats LPS injected via the tail vein de creased the IGF-I concentration in plasma, liver, and skeletal muscle (30-45%) and increased IGF-I content in kidney (similar to 3-fold). LP S also decreased IGF-I mRNA abundance in liver and muscle and increase d gene expression in kidney. Concomitantly, IGFBP-1 levels in plasma, liver, and muscle were markedly elevated by LPS. All these changes wer e associated with a greater than fourfold elevation in plasma corticos terone. Pretreatment of rats with the glucocorticoid receptor antagoni st RU-486 completely prevented or blunted the LPS-induced changes in I GF-I content in plasma, liver, muscle, and kidney. In liver and muscle RU-486 significantly attenuated the reduction in IGF-I mRNA abundance produced by LPS, but in kidney the LPS-induced increase in IGF-I mRNA was still evident. In contrast, pretreatment with RU-486 did not prev ent or attenuate the LPS-induced increase in IGFBP-1 levels in plasma, liver, or muscle. These data suggest that glucocorticoids play a majo r role in regulating IGF-I mRNA and peptide content in tissues in resp onse to LPS, but the increased IGFBP-1 in blood and tissues induced by LPS appears largely glucocorticoid independent.