Comparison of the biological effects of thyroxine and triiodothyronine in the rat.

To compare the biological effects of thyroxine (T4) and triiodothyronine (T3), the results of varying the production rates of T3 and T4 independently were evaluated. In one set of experiments, the responses of hypothyroid rats to thyroid hormones were measured in terms of weight gain, hepatic mitochondrial alpha-glycerophosphate dehydrogenase (alphaGPD) and serum TSH. T4 was given with, and without, 6-n-propylthiouracil (PTU) and alphaGPD activity paralleled, and could completely be accounted for, by the effect of the quantities of the T3 produced. The direct role of T3 production in the maintenance of hepatic alphaGPD activity was supported by finding normal serum T3 and alphaGPD activities, but reduced T4, in rats on low iodine diet for 2 months. Only after 4 months of iodine deficiency was alphaGPD reduced in the presence of a normal serum T3. These results suggest that T4 per se plays minimal role in this system. In contrast, there were significant effects of T4 administration on stimulation of weight gain and suppression of TSH release in hypothyroid animals which were not due to the T3 produced by peripheral conversion. While T3 given parenterally was about tenfold more potent than T4 in acute suppression of TSH, PTU retreatment did not alter the acute decrease in TSH after T4 which lasted for at least 22 h, as opposed to less than 7 h for T3. Despite the direct effect of T4 on TSH suppression , acute reduction in T3 in normal rats resulted in an elevation of serum TSH even though serum T4 concentrations were unchanged or even increased at this time. The results indicate that the thyrotroph, unlike the hepatocyte, can respond acutely to both increases and decreases in either T3 or T4 production. The differential sensitivities of various tissues to T3 and T4 indicate that the relative potencies of these two hormones must be defined experimentally in terms of a specific biological effect.