Regulation of insulin-like growth factor-I (IGF-I) and IGF-binding proteins by tumor necrosis factor

J. Fan, D. Char, G. J. Bagby, M. C. Gelato, C. H. Lang

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188 Scopus citations


The purpose of the present study was to determine 1) whether exogenous administration of tumor necrosis factor-α (TNF-α) alters insulin-like growth factor-I (IGF-I) and IGF-binding proteins (BPs) and 2) whether the enhanced endogenous production of TNF mediates the lipopolysaccharide (LPS)- induced changes in the IGF system. The overnight infusion of murine TNF-α reduced circulating concentrations of both growth hormone (GH) and IGF-I in fasted rats. Furthermore, TNF-α decreased IGF-I content in liver, gastrocnemius muscle, and pituitary. In contrast, TNF-α increased IGF-I content in kidney and brain. IGFBP-1 was increased in plasma, liver, and muscle in response to TNF-α. In a second study, rats were injected with LPS after treatment with a neutralizing anti-TNF antibody (Ab), and blood and tissues were collected 4 h later. In LPS-treated rats, plasma concentrations of GH and IGF-I were reduced. LPS also decreased the IGF-I content in liver and skeletal muscle and increased plasma, liver, and muscle concentrations of IGFBP-1. Pretreatment with anti-TNF Ab attenuated the LPS-induced reduction in IGF-I and the increased IGFBP-1 in plasma and liver and completely prevented the decrease in IGF-I observed in muscle. In contrast, the LPS- induced decrease in plasma GH and the increased IGFBP-1 observed in muscle were unaltered by the anti-TNF Ab. These results indicate that the GH/IGF axis is sensitive to TNF-α and that enhanced endogenous production of TNF mediates a major portion of the LPS-induced decrease in IGF-I in plasma, liver, and muscle, as well as a smaller portion of the concomitant elevation in IGFBP-1 in plasma and liver.

Original languageEnglish (US)
Pages (from-to)R1204-R1212
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number5 38-5
StatePublished - 1995

All Science Journal Classification (ASJC) codes

  • General Medicine


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