Extrathyroidal Thyroxine Formation in Completely Thyroidectomized Rats

Abstract

Thyroidectomized rats were injected daily with 5 mg of (K or Na) iodide for 2-4 weeks, a treatment shown in many previous experiments to have a marked thyromimetic effect on growth and other biological processes. Control thyroidectomized rats received simultaneously either NaCl or 5 [mu]g of iodide. Together with the last 3 or 7 injections, I131 was also administered in a daily dose of 500 [mu]c to both experimental and control groups. Plasma obtained 12-24 hr. after the last injection was dialyzed to remove Il31-, and concentrated butanol extracts were subjected to paper chromatography in 2 or 3 different solvents. Scans of the paper chromatograms prepared with plasma from the rats that received 5 mg of iodide daily showed unequivocal peaks corresponding to added T4 carrier in 5 of 8 experiments. Such peaks were not observed on corresponding chromatograms from the control rats. It was estimated that the rats injected with large doses of iodide produced sufficient T4 to maintain a plasma level as high as 13-25 [mu]g T4/ml, based on the assumption that the specific activity of I131 in the circulating T4 was equal to that of the injected iodide. Evidence is presented that at least 50% of the thyroidectomized rats selected for iodide injection were completely devoid of thyroid tissue. Since, under suitable conditions, the biological response to injected iodide occurs in 100% of the treated animals, it does not seem likely that residual thyroid tissue plays a role in the thyroxine-like action of iodide. Other evidence is also cited for this view. We conclude that thyroxine is formed at some extrathyroidal site(s) in thyroidectomized rats injected daily with 5 mg of iodide. The site(s) and mechanism of the reaction remain to be elucidated.