Interactions of iron deficiency, anemia, and thyroid hormone levels in the response of rats to cold exposure

We have earlier shown that iron-deficient rats have increased urinary norepinephrine (NE) excretion. They also have an exaggerated rise in urinary NE when placed in the cold, a stimulus known to cause increased NE excretion in normal rats. Nonetheless, they fail to maintain body temperature. We have now examined the thyroidal response to cold in iron-deficient rats. As others have shown, control rats had a rise in plasma levels of thyroxine (T4) and triiodothyroxine (T3) soon after entering the cold environment (4°C); they also maintained a rectal temperature above 36°C. In the iron-deficient rats, basal levels of T3 and T4 were normal, but there was little or no increase after 6 hr in the cold, and, as before, body temperatures fell. Injections of T3, 10 μg/kg, 15 min before cold exposure improved the ability of iron-deficient rats to maintain body temperature, but they still did not do as well as the controls. We conclude that the inability of iron-deficient rats to increase T3 levels after cold exposure is one factor in their poor resistance to cold. The defect could involve inability to augment thyroid secretion, impaired ability to convert T4 to T3 in peripheral tissues, or both. Preliminary data suggests that anemia is an important and perhaps critical factor in the cold sensitivity of iron deficiency. Transfusing iron-deficient rats from their usual hematocrit of 15–20 to one of 30 restores cold resistance to normal. Transfusion also allows a more normal thyroid response, with a rise in T3 and T4 levels, so thyroid hormones may be a factor in the improvement produced by transfusion. The mechanism by which T3 acts to improve resistance to acute cold is unknown; in contrast to many T3's effects that require protein synthesis and occur only after a several hour latent period, T3 may be able to act synergistically with NE to cause acute increases in thermogenesis.