Thyronamines and Derivatives: Physiological Relevance, Pharmacological Actions, and Future Research Directions
- PMID:27650974
- DOI: 10.1089/thy.2016.0178
Thyronamines and Derivatives: Physiological Relevance, Pharmacological Actions, and Future Research Directions
Abstract
Thyronamines (3-T1AM, T0AM) are endogenous compounds probably derived from L-thyroxine or its intermediate metabolites. Combined activities of intestinal deiodinases and ornithine decarboxylase generate 3-T1AM in vitro. Alternatively, 3-T1AM might be formed by the thyroid gland and secreted into the blood. 3-T1AM and T0AM concentrations have been determined by liquid chromatography-tandem mass spectrometry analysis (LC-MS/MS) in tissues, serum, and cell lines. However, large variations of 3-T1AM concentrations in human serum were reported by LC-MS/MS compared with a monoclonal antibody-based immunoassay. These differences might be caused by strong binding of the highly hydrophobic 3-T1AM to apolipoprotein B100. Pharmacological administration of 3-T1AM results in dose-dependent reversible effects on body temperature, cardiac function, energy metabolism, and neurological functions. The physiological relevance of these actions is unclear, but may occur at tissue concentrations close to the estimated endogenous concentrations of 3-T1AM or its metabolites T0AM or thyroacetic acid (TA1). A number of putative receptors, binding sites, and cellular target molecules mediating actions of the multi-target ligand 3-T1AM have been proposed. Among those are members of the trace amine associated receptor family, the adrenergic receptor ADRα2a, and the thermosensitive transient receptor potential melastatin 8 channel. Preclinical studies employing various animal experimental models are in progress, and more stable receptor-selective agonistic and antagonistic analogues of 3-T1AM are now available for testing. The potent endogenous thyroid hormone-derived biogenic amine 3-T1AM exerts marked cryogenic, metabolic, cardiac and central actions and represents a valuable lead compound linking endocrine, metabolic, and neuroscience research to advance development of new drugs.
Keywords: 3-iodothyronamine; G protein-coupled receptors; biogenic amine; cardiac effects; thermogenic effects; thyroid hormone metabolism.
Similar articles
- A validated LC-MS/MS method for cellular thyroid hormone metabolism: Uptake and turnover of mono-iodinated thyroid hormone metabolites by PCCL3 thyrocytes.Richards KH, Schanze N, Monk R, Rijntjes E, Rathmann D, Köhrle J.Richards KH, et al.PLoS One. 2017 Aug 24;12(8):e0183482. doi: 10.1371/journal.pone.0183482. eCollection 2017.PLoS One. 2017.PMID:28837607Free PMC article.
- Thyroid Hormones and Derivatives: Endogenous Thyroid Hormones and Their Targets.Köhrle J.Köhrle J.Methods Mol Biol. 2018;1801:85-104. doi: 10.1007/978-1-4939-7902-8_9.Methods Mol Biol. 2018.PMID:29892819Review.
- Cardiac actions of thyroid hormone metabolites.Rutigliano G, Zucchi R.Rutigliano G, et al.Mol Cell Endocrinol. 2017 Dec 15;458:76-81. doi: 10.1016/j.mce.2017.01.003. Epub 2017 Jan 7.Mol Cell Endocrinol. 2017.PMID:28069537Review.
- Endocrine, Metabolic and Pharmacological Effects of Thyronamines (TAM), Thyroacetic Acids (TA) and Thyroid Hormone Metabolites (THM) - Evidence from in vitro, Cellular, Experimental Animal and Human Studies.Homuth G, Lietzow J, Schanze N, Golchert J, Köhrle J.Homuth G, et al.Exp Clin Endocrinol Diabetes. 2020 Jun;128(6-07):401-413. doi: 10.1055/a-1139-9200. Epub 2020 May 25.Exp Clin Endocrinol Diabetes. 2020.PMID:32450582Review.
- Determination of 3-iodothyronamine (3-T1AM) in mouse liver using liquid chromatography-tandem mass spectrometry.Li ZM, Miller M, Gachkar S, Mittag J, Schriever SC, Pfluger PT, Schramm KW, De Angelis M.Li ZM, et al.J Chromatogr B Analyt Technol Biomed Life Sci. 2021 Feb 15;1165:122553. doi: 10.1016/j.jchromb.2021.122553. Epub 2021 Jan 18.J Chromatogr B Analyt Technol Biomed Life Sci. 2021.PMID:33503577
Cited by
- Non-Functional Trace Amine-Associated Receptor 1 Variants in Patients With Mental Disorders.Rutigliano G, Bräunig J, Del Grande C, Carnicelli V, Masci I, Merlino S, Kleinau G, Tessieri L, Pardossi S, Paisdzior S, Dell'Osso L, Biebermann H, Zucchi R.Rutigliano G, et al.Front Pharmacol. 2019 Sep 13;10:1027. doi: 10.3389/fphar.2019.01027. eCollection 2019.Front Pharmacol. 2019.PMID:31572197Free PMC article.
- Nonalcoholic Fatty Liver Disease and Hypercholesterolemia: Roles of Thyroid Hormones, Metabolites, and Agonists.Sinha RA, Bruinstroop E, Singh BK, Yen PM.Sinha RA, et al.Thyroid. 2019 Sep;29(9):1173-1191. doi: 10.1089/thy.2018.0664.Thyroid. 2019.PMID:31389309Free PMC article.Review.
- Canonical TSH Regulation of Cathepsin-Mediated Thyroglobulin Processing in the Thyroid Gland of Male Mice Requires Taar1 Expression.Qatato M, Szumska J, Skripnik V, Rijntjes E, Köhrle J, Brix K.Qatato M, et al.Front Pharmacol. 2018 Mar 20;9:221. doi: 10.3389/fphar.2018.00221. eCollection 2018.Front Pharmacol. 2018.PMID:29615904Free PMC article.
- Thyroid Hormone Analogues: An Update.Zucchi R.Zucchi R.Thyroid. 2020 Aug;30(8):1099-1105. doi: 10.1089/thy.2020.0071. Epub 2020 Apr 7.Thyroid. 2020.PMID:32098589Free PMC article.Review.
- In vivo Effects of Repeated Thyronamine Administration in Male C57BL/6J Mice.Harder L, Schanze N, Sarsenbayeva A, Kugel F, Köhrle J, Schomburg L, Mittag J, Hoefig CS.Harder L, et al.Eur Thyroid J. 2018 Jan;7(1):3-12. doi: 10.1159/000481856. Epub 2017 Dec 5.Eur Thyroid J. 2018.PMID:29594048Free PMC article.
Publication types
MeSH terms
Substances
Related information
LinkOut - more resources
Full Text Sources
Other Literature Sources