Dose response of protein turnover in rat skeletal muscle to triiodothyronine treatment.

Skeletal muscle protein turnover has been examined in thyroidectomized rats treated with 0, 0.3, 0.75, 2, 20 and 100 micrograms triidothyronine/day for 7 days by implanted osmotic minipump. Protein synthesis in gastrocnemius, plantaris and soleus muscle were measured in vivo by the constant infusion method and protein degradation estimated as the difference between gross and net rates of synthesis. Serum levels of triidothyronine (T3) and insulin were also measured in addition to oxygen consumption rates in some cases. Compared with untreated intact rats muscle growth rates were unchanged at 0.3, 0.75 and 2 micrograms T3/day and, judging by plasma T3 levels, 0.75 microgram T3/day was a replacement dose. Slowing of growth was evident in the untreated thyroidectomized rats mid-way through the 7 day experimental period (6-7 days after throidectomy). High doses of T3 (20 and 100 micrograms/day) promptly supressed growth but there was subsequent recovery. Protein synthesis and degradation were generally lower in the hypothyroid state and normal or elevated in the hyperthyroid state. The changes in protein synthesis were mediated by changes in both RNA concentration and RNA activity (protein synthesis per unit RNA). Gastrocnemius and plantaris muscles were most responsive in the hypothyroid range. Since protein synthesis is particularly depressed in these muscles in malnutrition, the fall in protein degradation induced by the lowered thyroid status in this condition will be an important adaptive response to conserve protein. The increased protein turnover in the hyperthyroid rats was most marked in the soleus muscle and it is argued that this is necessary to allow the changes in protein composition and metabolic character which occur in response to hyperthyroidism in this muscle.