Endocrine Abstracts

The ability of thyroid hormones to regulate body temperature is well established. While the active hormone T3 can act peripherally to induce thermogenesis in fat and muscle, it also acts centrally in the brain to increase body temperature through the sympathetic nervous system. Most remarkably, recent studies show that T3 treatment in mice causes an elevated body temperature even at 10°C, far below thermoneutrality, suggesting that the T3 effect constitutes pyrexia rather than hyperthermia. Therefore, mice with induced hyperthyroidism seem to have an altered temperature set point in the brain; however, the precise neuroanatomical substrate has remained unknown. The goal of this research project is to identify the brain region where T3 acts to regulate the body temperature setpoint. Using PET/CT scans of mice treated with T3, several candidate regions have been identified. Among these, the Zona Incerta (ZI), has been associated with the control of body temperature previously. To test whether this region constitutes the missing link between the central T3 effect and pyrexia, we studied the ZI using well-established mouse models. Preliminary data show no difference in cell number of dopaminergic neurons in the ZI when comparing offspring of wild-type mice to those of mice with a mutation in thyroid hormone receptor α1, indicating no developmental effect of thyroid hormones on ZI dopaminergic neurons. However, further studies will be needed to illuminate the acute actions of T3 in this enigmatic brain region.