Burn-induced changes in IGF-I and IGF-binding proteins are partially glucocorticoid dependent.
The purpose of the present study was to determine whether burn-induced changes in various components of the insulin-like growth factor (IGF) system are mediated by the actions of endogenous glucocorticoids or tumor necrosis factor (TNF). To address this aim, a 30% total body surface area full-thickness scald burn was produced in anesthetized rats, and the animals were studied 24 h later. Separate groups of time-matched control and burned rats were pretreated with either an antagonist to glucocorticoids (RU-486) or to TNF (TNF-binding protein; TNFBP). Thermal injury decreased the plasma concentration of IGF-I (38%) as well as the IGF-I mRNA abundance in muscle and kidney (31 and 48%, respectively). While RU-486 prevented the burn-induced decrease in plasma IGF-I, it did not ameliorate the reduction in tissue IGF-I mRNA. Burn increased the plasma concentration of IGF-binding protein (IGFBP)-1 as well as the mRNA content of IGFBP-1 in liver and kidney (15- to 20-fold). These burn-induced increases were partially or largely prevented by RU-486. In contrast, burn decreased the plasma concentration of IGFBP-3 (30%). Burn concomitantly decreased hepatic IGFBP-3 mRNA abundance (42%) but increased IGFBP-3 mRNA in kidney and muscle (50% and 10-fold, respectively). RU-486 largely prevented the burn-induced changes in IGFBP-3 mRNA in kidney and muscle but failed to attenuate the decreases in plasma and liver. Finally, burn injury decreased hepatic acid-labile subunit (ALS) mRNA by 80% and increased the mRNA content of IGFBP-related protein-1 (mac25) in liver by twofold, and these changes were not modified by pretreatment with RU-486. The above-mentioned changes in the IGF system were associated with a burn-induced decrease in muscle protein content that was prevented by RU-486. TNFBP failed to completely ameliorate any of the burn-induced changes in the IGF system. These results demonstrate that glucocorticoids, but not TNF, mediate many but not all of the burn-induced changes in the IGF system.
Lang
Charles H
CH
Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA. clang@psu.edu
Nystrom
Gerald J
GJ
Frost
Robert A
RA
D000818:Animals; D015152:Blotting, Northern; D002056:Burns / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D005938:Glucocorticoids / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006727:Hormone Antagonists / Q000494:pharmacology; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood / Q000235:genetics*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D007668:Kidney / Q000502:physiology; D008099:Liver / Q000502:physiology; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D009124:Muscle Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors; D047888:Receptors, Tumor Necrosis Factor, Type I; D013047:Specific Pathogen-Free Organisms; D053319:Tumor Necrosis Factor Decoy Receptors
D005938:Glucocorticoids; D006727:Hormone Antagonists; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D009124:Muscle Proteins; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D053319:Tumor Necrosis Factor Decoy Receptors; C069521:recombinant human tumor necrosis factor-binding protein-1; D015735:Mifepristone; D007334:Insulin-Like Growth Factor I