SPP 1629, Subproject: Non Classical Concepts of Thyroid Hormone Action in the Regulation of Body Temperature

Thyroid hormone is a classical regulator of peripheral thermogenesis. Recent studies however suggest that its actions in brain and the cardiovascular system are also of great relevance for the regulation of body temperature. Moreover, specific downstream metabolites of thyroid hormone have been identified, which also seem to have strong effects in temperature regulation.The proposed project now aims to test the hypothesis that the thermoregulatory effects of thyroid hormone and its metabolites 3-iodothyronamine and 3,5-diiodothyronine could in fact be mediated by central or cardiovascular actions, for instance by modulating heat dissipation. We will use a unique combination of in vivo and ex vivo studies to dissect the central and peripheral actions of the metabolites, including stereotaxic brain injections, wire myography to test vascular responses, and radiotelemetry to monitor body temperature and heart rate in the conscious and freely moving animal. Moreover, we will employ our established infrared thermography to quantify heat generation and heat dissipation in the whole animal. To unravel the underlying molecular mechanisms, gene expression studies will be conducted using microarray, qPCR and in situ hybridization / immunohistochemistry techniques.The results will provide novel and holistic insight into how thyroid hormone and its metabolites regulate body temperature, and how they affect the interplay between the different thermoregulatory systems. The proposed project therefore challenges the classical concepts of thyroid hormone in thermogenesis, and aims to unravel novel, non-classical mechansims of thyroid hormone action in the regulation of body temperature.