Correlation of serum triiodothyronine (T 3) and thyroxine (T 4) with biologic effects of thyroid hormone replacement in propylthiouracil-treated rats

Abstract

To study the role of T 4 to T 3 conversion in the biologic action of T 4, thyroidectomized, hypothyroid rats were given subcutaneous T 4 (0.8 or 1.6 μg/100g/day) with or without intraperitoneal propylthiouracil (PTU) (1 mg/100g/day). Rats were killed after 5, 10, 12, or 15 days of treatment and serum T 3 and T 4 levels were correlated with serum TSH, liver mitochondrial αGPD activity and weight gain. In rats killed at 5 days, PTU treatment resulted in higher serum T 4, lower serum T 3, and a markedly elevated serum T 4:T 3 ratio, demonstrating that PTU inhibits peripheral conversion of T 4 to T 3 in the rat. Despite higher T 4 levels, mean serum TSH was higher in the two groups receiving PTU as well as T 4. In rats receiving 0.8 μg T 4, growth rate was also slower with concomitant PTU administration. In other groups of rats treated with 0.8 μg T 4 for 10 and 15 days, PTU treatment resulted in similar differences in T 3, T 4, and T 4:T 3 ratios and serum TSH. At 15 days, rats treated with 0.8 μg T 4 + PTU had significantly lower αGPD activity than rats receiving 0.8 μg T 4 alone. PTU treatment had no effect on αGPD activity in rats maintained on 0.1 μg T 3/100g/day indicating that there was no inhibition of this biologic response to T 3 by this agent. PTU without T 4 had no significant effect on TSH, weight gain, or αGPD activity. In addition, the dialyzable fraction of T 3 and T 4 in serum was not altered by this agent. These data show that in animals treated with T 4, with and without PTU, TSH suppression, αGPD activity and growth correlate better with serum T 3 concentrations than with serum T 4. This suggests that for maximum biologic activity, T 4 must be converted to T 3.