3,5-DIIODO-L-THYRONINE AND 3,5,3'-TRIIODO-L-THYRONINE BOTH IMPROVE THE COLD TOLERANCE OF HYPOTHYROID RATS, BUT POSSIBLY VIA DIFFERENT MECHANISMS

The effects of 3,5-diiodo-L-thyronine (3,5-T2, 2.5-10 mu g/100 g BW) o n cold tolerance, energy expenditure and oxidative capacity of four me tabolically very active tissues (brown adipose tissue, skeletal muscle , liver and heart) were determined in hypothyroid, cold-exposed rats. Hypothyroid rats survived cold for only 3-4 days. 3,5-T2 improved surv ival dose dependently; with 10 mu g/100 g BW the rats survived 3 weeks (limit of observation). This effect was paralleled by an increased en ergy expenditure of the whole animal for the entire 3 weeks. Similar e ffects were observed in hypothyroid rats treated with 3,3',5-triiodo-L -thyronine (T3). 3,5-T2 stimulated the specific oxidative capacity (ex pressed as cytochrome oxidase activity per milligram protein) of all f our tissues dose dependently. When the oxidative capacity was expresse d as total activity (cytochrome oxidase activity times organ weight), the percentage increases were of the same order. T3 exerted similar ef fects, but the changes in total activity were much greater than in spe cific activity, indicating an effect on the tissue trophism. The effec t of 3,5-T2 on cold tolerance thus mimics the effect of T3, but via di fferent cellular mechanisms. T3 seems to act primarily on the trophism of the tissues, while 3,5-T2 may act directly on mitochondria without an effect on tissue trophism.