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Letter
Nature Medicine 10, 638 - 642 (2004)
Published online: 16 May 2004 | doi:10.1038/nm1051
3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone
Thomas S Scanlan1, Katherine L Suchland2,7, Matthew E Hart1,7, Grazia Chiellini3, Yong Huang4, Paul J Kruzich2, Sabina Frascarelli3, Dane A Crossley II2, James R Bunzow2, Simonetta Ronca-Testoni3, Emil T Lin4, Daniel Hatton5, Riccardo Zucchi3 & David K Grandy2,6
Abstract
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 TR
and TR
, whose activation controls normal vertebrate development and physiology1. T3-modulated transcription of target genes via activation of TR and TR 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 obscure2, 3. 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.
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