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Abstract
3-Iodothyronamine (T1AM), an endogenous thyroid hormone derivative, exhibits pharmacological effects opposite to thyroid hormone, including hypothermia, reduced cardiac function, and altered fuel utilization. Structural and metabolic similarities suggest T1AM may originate from thyroid hormone. Using isotope-labeled thyroid hormone and hypothyroid mice, LC-MS/MS analysis showed T1AM biosynthesis depends on thyroid gland function but is not derived from extrathyroidal metabolism. Following T1AM injection, extensive metabolism was observed, identifying novel serum metabolites—N-acetyl-T1AM and T1AM-glucuronide—along with sulfation and oxidative deamination. Several metabolites exceeded parent compound levels, indicating metabolism regulates T1AM distribution and action, paralleling thyroid hormone pathways.