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 elevations in glucocorticoids mediate the changes in insulin-like growth factor (IGF) 1 and IGF binding protein (IGFBP) 1 levels in plasma and tissues observed after in vivo administration of lipopolysaccharide (LPS). In overnight-fasted male rats LPS injected via the tail vein decreased the IGF-I concentration in plasma, liver, and skeletal muscle (30-45%) and increased IGF-I content in kidney (approximately 3-fold). LPS also decreased IGF-I mRNA abundance in liver and muscle and increased gene expression in kidney. Concomitantly, IGFBP-1 levels in plasma, liver, and muscle were markedly elevated by LPS. All these changes were associated with a greater than fourfold elevation in plasma corticosterone. Pretreatment of rats with the glucocorticoid receptor antagonist RU-486 completely prevented or blunted the LPS-induced changes in IGF-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 prevent or attenuate the LPS-induced increase in IGFBP-1 levels in plasma, liver, or muscle. These data suggest that glucocorticoids play a major role in regulating IGF-I mRNA and peptide content in tissues in response to LPS, but the increased IGFBP-1 in blood and tissues induced by LPS appears largely glucocorticoid independent.
Li
Y H
YH
Department of Surgery, State University of New York at Stony Brook 11794-8191, USA.
Fan
J
J
Lang
C H
CH
D000818:Animals; D004731:Endotoxins / Q000494:pharmacology*; D005938:Glucocorticoids / Q000502:physiology*; D006706:Homeostasis; D006727:Hormone Antagonists / Q000494:pharmacology; D006728:Hormones / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood* / Q000187:drug effects; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000032:analysis* / Q000187:drug effects / Q000235:genetics; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D013997:Time Factors
D004731:Endotoxins; D005938:Glucocorticoids; D006727:Hormone Antagonists; D006728:Hormones; D018970:Insulin-Like Growth Factor Binding Protein 1; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D007334:Insulin-Like Growth Factor I