3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone

Thomas S. Scanlan, Katherine L. Suchland, Matthew E. Hart, Grazia Chiellini, Yong Huang, Paul J. Kruzich, Sabina Frascarelli, Dane A. Crossley, James R. Bunzow, Simonetta Ronca-Testoni, Emil T. Lin, Daniel Hatton, Riccardo Zucchi, David K. Grandy

Research output: Contribution to journalArticlepeer-review

363 Scopus citations


Thyroxine (T4) is the predominant form of thyroid hormone (TH). Hyperthyroidism, a condition associated with excess TH, is characterized by increases in metabolic rate, core body temperature and cardiac performance. In target tissues, T4 is enzymatically deiodinated to 3,5,3′-triiodothyronine (T3), a high-affinity ligand for the nuclear TH receptors TRα and TRβ, whose activation controls normal vertebrate development and physiology. T3-modulated transcription of target genes via activation of TRα and TRβ is a slow process, the effects of which manifest over hours and days. Although rapidly occurring effects of TH have been documented, the molecules that mediate these non-genomic effects remain obscure. Here we report the discovery of 3-iodothyronamine (T1AM), a naturally occurring derivative of TH that in vitro is a potent agonist of the G protein-coupled trace amine receptor TAR1. Administering T1AM in vivo induces profound hypothermia and bradycardia within minutes. T1AM treatment also rapidly reduces cardiac output in an ex vivo working heart preparation. These results suggest the existence of a new signaling pathway, stimulation of which leads to rapid physiological and behavioral consequences that are opposite those associated with excess TH.

Original languageEnglish (US)
Pages (from-to)638-642
Number of pages5
JournalNature medicine
Issue number6
StatePublished - Jun 2004
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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