Extrathyroidal conversion of thyroxine to 3,5,3'-triiodothyronine in cold-acclimated thyroxine-maintained thyroidectomized rats.

Chronic exposure of rats to cold (4 degrees C) leads to thyroid gland hyperactivity as a compensatory mechanism for activating body heat production. There is increased extrathyroidal production of T3 from T4 in parallel to thyroid hormone hypersecretion. Since the 5'-deiodination (5'-D) of T4 can be modulated by thyroid hormones, it has been suggested that the increased thyroid hormone secretion may activate the 5'-D enzymatic pathway leading to increased extrathyroidal T3 production. In an attempt to explore this possibility, T4 to T3 conversion was studied in liver and kidney homogenates of thyroidectomized rats which received T4 (0.5 to 50 micrograms/100 g body weight per day) for 10 days. Tissue homogenates were incubated with T4 (5 micrograms) for 2 h and the T3 generated was measured by RIA as an index of the activity of the 5'-D pathway. A direct relationship between T4 dose and the production of T3 by the homogenate was observed. 5'-D activity was significantly decreased in hypothyroid rats and greatly increased in hyperthyroid rats. Thyroidectomized rats treated with a replacement dose of T4 (1 microgram/100 g body weight/day) were exposed to 4 degrees C for 60 days. Despite the absence of the thyroid gland, increased 5'-D activity was observed in both liver and kidney homogenates compared to both intact and T4-treated thyroidectomized rats maintained at 25 degrees C. We conclude that chronic cold exposure of rats stimulates 5'-D activity which is independent of the concomitant thyroid gland hyperactivity.