Thyroid Hormones Influence Starvation-Induced Hepatic Protein Loss in the Rat: Possible Role of Thyroid Hormones in the Generation of Labile Protein*

The possibility that the starvation-induced fall in serum T3 serves to minimize protein catabolism prompted us to investigate the general relationship between thyroid hormone status and hepatic protein loss in starved rats. During 5 days of starvation, euthyroid (Eu) rats lost 426 ± 13 mg/100 g BW (mean ± SEM), representing 54% of the initial hepatic protein. In contrast, thyroidectomized rats lost only 111 ± 3 mg/100 g BW, representing 22% of the total. Concomitant experiments indicated that these results could not be attributed to differences in age or weight of the animals. Moreover, studies of food restriction in Eu animals suggested that these findings were not a direct effect of diminished food consumption in hypothyroid animals. When graded doses of T3 (100, 150, and 300 ng/100 g BW) were administered to thyroidectomized rats, progressive increases in starvation-induced protein loss to 180 ± 22, 232 ± 18, and 308 ± 9 mg/100 g BW, respectively, were observed. On the contrary, pretreatment of Eu rats for 8 days before and during 5 days of starvation with 300 ng T3/100 g BW caused no measurable differences in hepatic protein loss or urinary urea excretion. Our data thus provided no evidence that an acute lowering of T3 resulted in a protein-sparing effect in the starved rat. A possible explanation for these findings was provided by the observation that the residual hepatic protein mass in all animals, regardless of age or thyroid status, was remarkably constant when expressed per 100 g BW (402 ± 56 mg/100 g BW). This suggested that hepatic protein could be divided into stable and labile pools. Experiments designed to assess the kinetics of hepatic protein depletion confirmed the existence of these pools. We postulate that thyroid hormones are essential for the generation of the labile pool, which may serve as the immediate source of amino acids for gluconeogenesis and protein synthesis during acute starvation. Differences in hepatic protein loss of animals, therefore, may be a reflection of variation in preexisting labile pools rather than in the plasma T3 concentration during the immediate starvation period.