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

Thomas (Tom) 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 Grandy

    Research output: Contribution to journalArticle

    311 Citations (Scopus)

    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 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
    Volume10
    Issue number6
    DOIs
    StatePublished - Jun 2004

    Fingerprint

    Thyroid Hormones
    Derivatives
    Chemical activation
    Hypothermia
    Thyroid Hormone Receptors
    Physiology
    Triiodothyronine
    Hyperthyroidism
    Transcription
    Bradycardia
    Cytoplasmic and Nuclear Receptors
    Body Temperature
    Thyroxine
    GTP-Binding Proteins
    Cardiac Output
    Transcriptional Activation
    Amines
    Vertebrates
    Genes
    3-iodothyronamine

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)
    • Medicine(all)

    Cite this

    Scanlan, T. T., Suchland, K. L., Hart, M. E., Chiellini, G., Huang, Y., Kruzich, P. J., ... Grandy, D. (2004). 3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone. Nature Medicine, 10(6), 638-642. https://doi.org/10.1038/nm1051

    3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone. / Scanlan, Thomas (Tom); Suchland, Katherine L.; Hart, Matthew E.; Chiellini, Grazia; Huang, Yong; Kruzich, Paul J.; Frascarelli, Sabina; Crossley, Dane A.; Bunzow, James R.; Ronca-Testoni, Simonetta; Lin, Emil T.; Hatton, Daniel; Zucchi, Riccardo; Grandy, David.

    In: Nature Medicine, Vol. 10, No. 6, 06.2004, p. 638-642.

    Research output: Contribution to journalArticle

    Scanlan, TT, Suchland, KL, Hart, ME, Chiellini, G, Huang, Y, Kruzich, PJ, Frascarelli, S, Crossley, DA, Bunzow, JR, Ronca-Testoni, S, Lin, ET, Hatton, D, Zucchi, R & Grandy, D 2004, '3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone', Nature Medicine, vol. 10, no. 6, pp. 638-642. https://doi.org/10.1038/nm1051
    Scanlan TT, Suchland KL, Hart ME, Chiellini G, Huang Y, Kruzich PJ et al. 3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone. Nature Medicine. 2004 Jun;10(6):638-642. https://doi.org/10.1038/nm1051
    Scanlan, Thomas (Tom) ; Suchland, Katherine L. ; Hart, Matthew E. ; Chiellini, Grazia ; Huang, Yong ; Kruzich, Paul J. ; Frascarelli, Sabina ; Crossley, Dane A. ; Bunzow, James R. ; Ronca-Testoni, Simonetta ; Lin, Emil T. ; Hatton, Daniel ; Zucchi, Riccardo ; Grandy, David. / 3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone. In: Nature Medicine. 2004 ; Vol. 10, No. 6. pp. 638-642.
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