Biomarkers of Thyronamine Action (BioTAct)

甲状腺胺是最近重新发现的一类对人类健康和医学应用具有潜在高度重要性的内源性激素。除了一些关于动物模型中令人印象深刻的强烈生理作用的初步报道外，不同甲状腺胺的确切分子作用模式尚不清楚。甲状腺胺可以抵消经典的甲状腺激素T3和T4的作用。例如，将3-碘甲状腺原氨酸（3-T1 AM）注射到小鼠中降低了葡萄糖并增加了脂质代谢，并降低了代谢率、体温、变时性和变时性以及能量周转的其他测量。除了对生物体的这些全身性影响外，尚不了解负责的信号传导途径，并且缺少甲状腺原氨酸（TAM）作用的分子生物标志物。我们已经鉴定了TAM应答细胞模型。现在，我们的目标是采用系统的筛选方法来确定TAM作用的分子靶点。将结合途径报告基因测定、全局基因表达分析、候选基因方法和细胞分化的生物学读数进行生物标记物鉴定。候选分子将经过验证并用于追踪负责其TAM依赖性调节的途径。长期目标是鉴定合适的生物标志物，其可以从实验动物和人的血清样品中测量，作为个体TAM状态的诊断读数。

Thyronamines are a recently re-discovered class of endogenous hormones of potential high importance for human health and medical applications. Besides some initial reports on impressively strong physiological effects in animal models, the exact molecular mode of action of the different thyronamines is not understood. Thyronamines can counteract the effects of the classical thyroid hormones T3 and T4. As an example, injection of 3-iodothyronamine (3-T1AM) into mice reduces glucose and increases lipid metabolism, and reduces metabolic rate, body temperature, ino- and chronotropy and other measures of energy turnover. Besides these systemic effects on the organism, the responsible signalling pathways are not understood as well as molecular biomarkers of thyronamine (TAM) action are missing. We have identified TAM-responsive cell models. Now we aim to employ a systematic screening approach to identify molecular targets of TAM action. Pathway reporter assays, global gene expression analyses, candidate gene approaches and biological readouts of cell differentiation will be combined for bio-marker identification. Molecular candidates will be validated and used to track the pathways responsible for their TAM-dependent regulation. Long-term aim is the identification of suitable biomarkers that can be measured from serum samples of experimental animals and humans as diagnostic readouts for the individual TAM status.