Correlation of serum triiodothyronine (T3) and thyroxine (T4) with biologic effects of thyroid hormone replacement in propylthiouracil-treated rats

Abstract

To study the role of T4 to T3 conversion in the biologic action of T4, thyroidectomized, hypothyroid rats were given subcutaneous T4 (0.8 or 1.6 mug/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 T3 and T4 levels were correlated with serum TSH, liver mitochondrial alphaGPD activity and weight gain. In rats killed at 5 days, PTU treatment resulted in higher serum T4, lower serum T3, and a markedly elevated serum T4:T3 ratio, demonstrating that PTU inhibits peripheral conversion of T4 to T3 in the rat. Despite higher T4 levels, mean serum TSH was higher in the two groups receiving PTU as well as T4. In rats receiving 0.8 mug T4, growth rate was also slower with concomitant PTU administration. In other groups of rats treated with 0.8 mug T4 for 10 and 15 days, PTU treatment resulted in similar differences in T3, T4, and T4:T3 ratios and serum TSH. At 15 days, rats treated with 0.8 mug T4 mptu had significantly lower alphaGPD activity than rats receiving 0.8 mug T4 alone. PTU treatment had no effect on alphaGPD activity in rats maintained on 0.1 mug T3/100g/day indicating that there was no inhibition of this biologic response to T3 by this agent. PTU without T4 had no significant effect on TSH, weight gain, or alphaGPD activity. In addition, the dialyzable fraction of T3 and T4 in serum was not altered by this agent. These data show that in animals treated with T4, with and without PTU, TSH suppression, alphaGPD activity and growth correlate better with serum T3 concentrations than with serum T4. This suggests that for maximum biologic activity, T4 must be converted to T3.