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- Title
3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone.
- Authors
Scanlan, Thomas S.; Suchland, Katherine L.; Hart, Matthew E.; Chiellini, Grazia; Yong Huang; Kruzich, Paul J.; Frascarelli, Sabina; Crossley II, Dane A.; Bunzow, James R.; Ronca-Testoni, Simonetta; Lin, Emil T.; Hatton, Daniel; Zucchi, Riccardo; Grandy, David K.
- 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 TRa and TRß, whose activation controls normal vertebrate development and physiology. T3-modulated transcription of target genes via activation of TRa and TRß 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.
- Subjects
THYROXINE; THYROGLOBULIN; THYROID hormones; HYPERTHYROIDISM; THYROID diseases; BIOCHEMISTRY
- Publication
Nature Medicine, 2004, Vol 10, Issue 6, p638
- ISSN
1078-8956
- Publication type
Article
- DOI
10.1038/nm1051