Effect of T3 on Muscle Protein Turnover and Function

Carter, William

Abstract

Studies in this proposal will evaluate the role of T3 in regulating protein turnover, structure, and function in cardiac and skeletal muscle. To examine the apparent paradox of increased T3 levels and decreased skeletal muscle protein turnover in protein depleted rats, free T3 levels will be measured and T3 impact on muscle will be estimated by determining V1 isomyosin content and myosin ATPase activity in the ventricular myocardium. If effective T3 level are reduced in protein depleted animals, the reduction will be prevented and the response of muscle protein turnover evaluated. To determine whether the reduced cardiac output and ventricular myosin ATPase activity in senescent rats is related to decreased T3 levels or decreased response of ventricular V1 isomyosin to T3, the effect of various doses of T3 on V1 isomyosin content, myosin ATPase activity, and cardiac output will be compared in senescent and young rats. A partial or total failure of T3 to alter the isomyosin profile in the aged ventricle may predispose elderly subjects with thyrotoxicosis to heart failure. To determine the role of T3 in causing the decreased V1 isomyosin content in ventricular hypertrophy due to pressure overload, serum T3 levels following aortic constriction will be measured, the response of V1 isomyosin in the hypertrophied ventricle to various doses of T3 will be determined, and T3 binding to nuclear receptors in the hypertrophied ventricle will be evaluated. Since T3 influences the isomyosin distribution in the ventricle but not in the atrium, T3 effects on actin and myosin heavy chain turnover in the atria and ventricles will be compared. This study will show whether T3 induced changes in the turnover of specific contractile proteins can be related to changes in muscle structure and function. The current proposal will: 1) shift from dietary thermogenesis back to T3 effects on muscle metabolism; 2) The metabolic significance of elevated T3 levels in protein depleted rats will be investigated; and 3) Osmotic minipumps will be used to provide a more physiologic means of administering T3.