Interaction between corticosterone and tumor necrosis factor stimulated protein breakdown in rat skeletal muscle, similar to sepsis.
Protein synthesis and breakdown rates were determined in incubated extensor digitorum longus muscles of rats treated with tumor necrosis factor (TNF; 20 micrograms/100 gm body weight), corticosterone (20 mg/100 gm body weight), or a combination of the two substances. Protein synthesis was measured as incorporation of carbon 14-labeled phenylalanine into protein. Total and myofibrillar protein breakdown rates were assessed as release of tyrosine and 3-methylhistidine, respectively. Administration of TNF alone did not affect muscle protein turnover rates. Corticosterone inhibited muscle protein synthesis and stimulated total and myofibrillar protein breakdown. When TNF was administered together with corticosterone, total and myofibrillar protein breakdown rates were increased further compared with rats treated with corticosterone alone. Because plasma corticosterone levels in rats treated with both TNF and the glucocorticoid were higher than in animals treated with corticosterone alone, it is possible that muscle proteolysis noted after TNF, injected together with costicosterone, was caused by the high glucocorticoid levels. To test that hypothesis, corticosterone alone or in combination with TNF was injected in rats that had undergone adrenalectomy. In these experiments, TNF did not increase plasma corticosterone levels or muscle protein breakdown rates. The results suggest that muscle catabolism induced by administration of TNF is mediated by glucocorticoids.
Hall-Angerås
M
M
Department of Surgery, University of Cincinnati, Ohio 45267-0558.
Angerås
U
U
Zamir
O
O
Hasselgren
P O
PO
Fischer
J E
JE
D000315:Adrenalectomy; D000818:Animals; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology*; D004347:Drug Interactions; D007239:Infections / Q000378:metabolism*; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism*; D009210:Myofibrils / Q000378:metabolism; D010649:Phenylalanine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D009124:Muscle Proteins; D014409:Tumor Necrosis Factor-alpha; D010649:Phenylalanine; D003345:Corticosterone