Regulation of insulin-like growth factor (IGF)-I mRNA and peptide and IGF-binding proteins by interleukin-1.
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-1 beta. IL-1 beta 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-1 beta-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-1 beta. Furthermore, pretreatment with RU-486 did not completely prevent the IL-1 beta-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-1 beta, and these changes were also not prevented by RU-486. These results indicate that the inflammatory cytokine IL-1 beta is capable of influencing multiple components of the IGF system. Whereas the enhanced endogenous production of glucocorticoids appears to mediate the IL-1 beta-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.
Fan
J
J
Department of Surgery, State University of New York at Stony Brook 11794-8191, USA.
Wojnar
M M
MM
Theodorakis
M
M
Lang
C H
CH
D000818:Animals; D003345:Corticosterone / Q000097:blood; D006801:Humans; D007275:Injections, Intravenous; D018969:Insulin-Like Growth Factor Binding Proteins / Q000032:analysis / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007375:Interleukin-1 / Q000008:administration & dosage*; D008297:Male; D009928:Organ Specificity; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage
D018969:Insulin-Like Growth Factor Binding Proteins; D007375:Interleukin-1; D012333:RNA, Messenger; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D003345:Corticosterone