Non Classical Concepts of Thyroid Hormone Action in the Regulation of Body Temperature

甲状腺激素在体温调节中的作用的非经典概念

• 批准号: 279770833
• 负责人: Professor Dr. Jens Mittag
• 金额: --
• 依托单位: Zentrum für Gehirn, Hormone und Verhalten (CBBM)
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/279770833?language=en
• 关键词: Non; Classical; Concepts; Thyroid; Hormone

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.

甲状腺激素是外周产热的经典调节因子。然而，最近的研究表明，它在大脑和心血管系统中的作用也与体温调节密切相关。此外，还发现了甲状腺激素的下游代谢物，这些代谢物似乎在体温调节方面也有很强的作用。本项目的目的是验证甲状腺激素及其代谢物3-碘甲状腺原氨酸和3，5-二碘甲状腺原氨酸的体温调节作用实际上可能是通过中枢或心血管作用介导的假说，例如通过调节散热。我们将使用体内和离体研究的独特组合来剖析代谢物的中枢和外周作用，包括脑立体定位注射、测试血管反应的钢丝肌造影和监测清醒和自由移动动物体温和心率的无线电遥测。此外，我们将使用我们建立的红外热成像来量化整个动物的产热和散热。为了揭示潜在的分子机制，将使用微阵列、qPCR和原位杂交/免疫组织化学技术进行基因表达研究。研究结果将为甲状腺激素及其代谢物如何调节体温以及它们如何影响不同体温调节系统之间的相互作用提供新的和全面的见解。因此，拟议中的项目挑战甲状腺激素在产热中的经典概念，旨在揭示甲状腺激素在调节体温中的作用的新的非经典机制。