Biomarkers of Thyronamine Action (BioTAct)

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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.