Studies on hypothermia and thyroid function in the obese (ob/ob) mouse.

This paper examined some of the relations between thyroid function and the hypothermia of the obese mouse after exposure to the cold. The fall in body temperature of obese mice treated with T3 was less rapid than in untreated obese mice. In the lean mouse, the induction of hypothyroidism by pretreatment with PTU enhanced the rate of fall of body temperature of these mice while in the cold. Circulating levels of TSH were the same in lean and obese mice at 28 t and after exposure to 24°C, TSH in obese mouse was increased more than in lean mouse, but maximal response of TSH to cold at 4°C was same between lean and obese mouse.The TSH response to TRH was significantly less in the obese mice. The thyroidal 125I-uptake was also lower in the obese mouse. The lowered uptake was, however, accompanied by a higher turnover rate as indicated by the more rapid appearance of radioactivity in BEI. Pretreatment with TSH increased the size of the thyroid gland, the uptake of radioactive iodine, the concentration of T4 and T3 in the serum, but did not alter the rapid decline in body temperature of the obese mouse after exposure to the cold. The possibility of an impaired response to exogenous T3 was examined by rendering lean and obese mice hypothyroid with injections of methimazole and then giving T3. The level of plasma T3 in obese mouse was higher than in lean mouse on daily supprement of T3 15mg and and the level of plasma TSH in obese mouse was lower on daily supprement of T3 50ng. However, not even the highest dose of T3 in the obese mice prevented completely the fall in body temperature. These studies suggest that peripheral unresponsiveness to the actions of triiodothyronine may be a major reason for the hypometabolism and hypothermia in these animals.