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
Georg Homuth
2
Department of Functional Genomics, University Medicine Greifswald,
Interfaculty Institute for Genetics and Functional Genomics, Greifswald,
Germany
,
Julika Lietzow
1
Charité – Universitätsmedizin Berlin, Corporate
Member of Freie Universität Berlin, Humboldt-Universität zu
Berlin, and Berlin Institute of Health, Berlin, Germany Institut für
Experimentelle Endokrinologie, Berlin, Germany
,
Nancy Schanze
1
Charité – Universitätsmedizin Berlin, Corporate
Member of Freie Universität Berlin, Humboldt-Universität zu
Berlin, and Berlin Institute of Health, Berlin, Germany Institut für
Experimentelle Endokrinologie, Berlin, Germany
,
Janine Golchert
2
Department of Functional Genomics, University Medicine Greifswald,
Interfaculty Institute for Genetics and Functional Genomics, Greifswald,
Germany
1
Charité – Universitätsmedizin Berlin, Corporate
Member of Freie Universität Berlin, Humboldt-Universität zu
Berlin, and Berlin Institute of Health, Berlin, Germany Institut für
Experimentelle Endokrinologie, Berlin, Germany
› Author AffiliationsFunding: Funding for this project has been received from the Deutsche
Forschungsgemeinschaft DFG in the framework of the Priority Programme
ThyroidTransAct SPP 1629 (TTA KO 922/16–2 to KJ and TTA HO
2140/6–2 to GH).
Thyroid hormone metabolites (THM) with few or no iodine substituents such as
3,5-T2, the thyronamines 3-T1AM and T0AM, and their oxidation products, the
thyroacetic acids (TA) formed by monoamine oxidases, have recently attracted
major interest due to their metabolic actions which are in part distinct from
those of the classical thyromimetic hormone T3, the major ligand of T3
receptors. This review compiles and discusses in vitro effects of 3,5-T2,
TAM and TA reported for thyrocytes, pancreatic islets and hepatocytes as well as
findings from in vivo studies in mouse models after single or repeated
administration of pharmacological doses of these agents. Comparison of the
3,5-T2 effects on the transcriptome with not yet published proteome data in
livers of obese mice on high fat diet indicate a distinct anti-steatotic effect
of this THM. Furthermore, uptake, metabolism, and cellular actions via various
receptors such as trace amine-associated receptors (TAAR), alpha-adrenergic,
GPCR and T3 receptors are discussed. Studies on postulated pathways of
biosynthesis of 3-T1AM, its effects on the HPT-axis and thyroid gland as well as
insulin secretion are reviewed. 3-T1AM also acts on hepatocytes and interferes
with TRPM8-dependent signaling in human cell lines related to the eye
compartment. Human studies are presented which address potential biosynthesis
routes of 3,5-T2 and 3-T1AM from THM precursors, especially T3. The current
state of diagnostic analytics of these minor THM in human blood is portrayed
comparing and critically discussing the still divergent findings based on
classical immunoassay and recently developed liquid-chromatography/mass-
spectrometry methods, which allow quantification of the thyronome spectrum from
one single small volume serum sample. The clinical perspectives of use and
potential abuse of these biologically active THM is addressed.
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