Endocrine Abstracts

Thyroid hormone is long known for its profound effect on body temperature regulation. Patients suffering from hyperthyroidism display elevated body temperature and are sensitive to heat, while hypothyroid patients are cold sensitive. The precise regulation of body temperature by thyroid hormone, however, has been incompletely understood. In our recent studies, we have studied the thermogenic effects of the hormone in a mouse model in detail. We observed that the body temperature increase induced by the hormone persisted independent of the environmental temperature, demonstrating that it constituted an upregulation of the central set point comparable to fever. However, there was a parallel increase in peripheral thermogenesis, which at room temperature even exceeded the elevated set point, causing a hyperthermia response. Using mice lacking the thermogenic uncoupling protein 1, we subsequently demonstrated that this hyperthermia was not caused by brown or beige fat thermogenesis, but likely originated in muscle. To test the central set point hypothesis further, we studied mice lacking the thyroid hormone transporters MCT8 and OATP1C1. Consequently, these animals display a severely hypothyroid brain in the presence of systemically elevated T3 levels. Interestingly, the double knockout mice did not present with an elevated body temperature, demonstrating that the central actions of the hormone are required for the fever phenotype observed in hyperthyroidism. Taken together, our work shows that thyroid hormone simultaneously acts thermogenic in the periphery and pyrexic in the brain, which is of particular interest for the role this hormone may have played in the evolutionary development of endothermy.