Regulation of insulin-like growth factor (IGF)-I mRNA and peptide and IGF-binding proteins by interleukin-1

Jie Fan, Margaret M. Wojnar, Matthew Theodorakis, Charles H. Lang

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The purpose of the present study was to determine whether interleukin (IL)-1 would alter the insulin-like growth factor (IGF) system in rats and whether this change was mediated by glucocorticoids. The IGF-I concentration was decreased in plasma (32%), liver (35%), skeletal muscle (40-50% depending on fiber type), pituitary (36%), and brain (52%), and increased in kidney (73%) 6 h after intravenous injection of IL-1β. IL-1β also decreased IGF-I mRNA levels in liver and muscle and increased expression in kidney. These changes were associated with a >2.5-fold elevation in plasma corticosterone levels. Pretreatment of rats with the glucocorticoid receptor antagonist RU-486 prevented the IL-1β-induced decrease in plasma and liver IGF-I concentration and the reduction in hepatic IGF-I mRNA expression. In contrast, RU-486 did not significantly attenuate the fall in IGF-I content in skeletal muscle, heart, brain, or pituitary or the increase in IGF-I observed in kidney after IL-1β. Furthermore, pretreatment with RU-486 did not completely prevent the IL-1β-induced decrease in IGF-I mRNA in skeletal muscle. The concentration of both IGF-binding protein (BP)-1 and BP-2 was increased in plasma, liver, and muscle in response to IL-1β, and these changes were also not prevented by RU-486. These results indicate that the inflammatory cytokine IL-1β is capable of influencing multiple components of the IGF system. Whereas the enhanced endogenous production of glucocorticoids appears to mediate the IL-1β-induced decrease in IGF-I synthesis in liver, the changes in IGF-I content observed in other tissues and the increase in IGFBP-1 and IGFBP-2 appear to be largely glucocorticoid independent.

Original languageEnglish (US)
Pages (from-to)R621-R629
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number3 39-3
StatePublished - 1996

All Science Journal Classification (ASJC) codes

  • General Medicine


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