The role of insulin and thyroid hormones in the regulation of muscle growth and protein turnover in response to dietary protein in the rat.

1. We have investigated the relations between changes in plasma insulin and 3,5,3'-triiodothyronine (T3), and muscle growth and protein turnover in the rat in response to diets of varying protein concentrations. 2. Young rats were fed ad lib. on a control (180 g casein/kg) diet or low-protein diets containing 80, 45 and 0 g casein/kg in four separate experiments. Measurements were made of food intakes, muscle and body-weight growth rates, muscle protein turnover in vivo, plasma insulin, and plasma free and total T3. 3. The food intakes of the 80 and 45 g casein/kg diet groups were variable, with the 80 g casein/kg diet group consuming either the same or more than the controls, and the 45 g casein/kg diet group consuming less or more than the controls. Body-weight and skeletal-muscle growth rates varied with the protein but not energy intakes, which in turn reflected both dietary composition and the food intake, with the hyperphagic 80 g casein/kg diet group of rats growing almost normally and the 0 g casein/kg diet group losing body-weight and muscle mass. 4. Changes in rates of muscle growth were accompanied by parallel changes in rates of protein synthesis and degradation, as well as parallel changes in concentrations of plasma insulin and free T3, to the extent that all these variables were highly correlated with each other. 5. Partial correlation analysis was used to separate interactions between variables. This indicated that dietary energy had no identifiable influence on muscle growth. In contrast dietary protein appeared to stimulate muscle growth directly by increasing muscle RNA content and inhibiting proteolysis, as well as increasing insulin and free T3 levels. Insulin and free T3 stimulated each other as well as muscle protein turnover; insulin stimulating the RNA activity particularly at low insulin levels, free T3 stimulating the RNA content and both hormones stimulating proteolysis. 6. These apparent relations are shown to be consistent in the main part with previous studies of the mechanism of action of insulin and T3, but the possibility cannot be discounted that other anabolic hormones not measured in these studies are involved, particularly in the apparent direct influence of dietary protein on muscle.