Thyroxine: studies concerning its intrinsic physiological activity

The importance of the monodeiodination of T4 to T3 in the physiological action of T4 was explored by assessing the role of T4 in maintaining prophylthiouracil (PTU)-treated rats during exposure to 4 degrees C. (PTU inhibits both thyroid hormone biosynthesis and T4 to T3 conversion in peripheral tissues.) Firstly, the effects of cold exposure on the metabolism of T4 in control and PTU-treated rats equilibrated with [125I]T4 (2 microgram/100 g b. w./day) were determined. PTU was administered in the food (2 mg/g food). In control rats, no significant changes in T4 metabolism occurred during 3 days at 4 degrees C. Urinary 125I was greatly decreased in PTU-treated rats. Exposure of these rats to cold resulted in some increase but values were still 50% below normal. Secondly, four groups of rats were exposed to cold: control; PTU-treated; T4-treated; PTU + T4-treated. Control and T4-treated rats survived. PTU-treated rats died unless T4 was administered. Radioimmunoassay of T4 and T3 indicated significant concentrations of T3 in sera of rats from all but the PTU + T4 group. These results suggest that T4 permits survival in the cold-exposed PTU-treated rat without being converted to T3 and thus they support the concept that T4 has intrinsic biological activity.