Thyronamines: beyond T4 and T3
In 2004, we reported the discovery of a new signaling molecule chemically related to thyroid hormones called 3-iodothyronamine (T1AM). T1AM is formally a decarboxylated and deiodinated derivative of thyroxine (T4) and was detected in tissues and circulation of rodents. Single-dose administration of T1AM to mice resulted in unique biological activities including hypothermia, bradycardia, and hyperglycemia. The T1AM-induced hyperthermia could have useful therapeutic applications as T1AM has been found to be neuroprotective against stroke in mice. In hibernating rodents single-dose T1AM induces a dramatic shift in energy utilization away from carbohydrates and toward lipids. T1AM does not bind to or activate thyroid hormone receptors (TRα, TRβ), yet does bind and/or activate a few G protein-coupled receptors (GPCRs) of the biogenic amine receptor family including trace amine-associated receptor 1 (TAAR1), α-adrenergic receptor 2a (Adra2a), and serotonin receptor 2c (5HT2c). This lecture will cover the developments in this area and highlight recent work on T1AM serum protein binding and distribution, and biological effects from chronic T1AM treatment in normal and diet-induced obese mice.