Thyroid hormones and derivatives: endogenous thyroid hormones and their targets
Abstract
More than a century after the discovery of L-Thyroxine, the main thyroid hormone secreted solely by the thyroid gland, several metabolites of this iodinated, tyrosine-derived ancestral hormone have been identified. These are utilized as hormones during development, differentiation, metamorphosis, and regulation of most biochemical reactions in vertebrates and their precursor species. Among those metabolites are the thyromimetically active 3,3',5-Triiodo-L-thyronine (T3) and 3,5-Diiodo-L-thronine, reverse-T3 (3,3',5'-Triiodo-L-thyronine) with still unclear function, the recently re-discovered thyronamines (e.g., 3-Iodo-thyronamine), which exert in part T3-antagonistic functions, the thyroacetic acids (e.g., Tetrac and Triac), as well as various sulfated or glucuronidated metabolites of this panel of iodinated signaling compounds. In the blood most of these hydrophobic metabolites are tightly bound to the serum distributor proteins thyroxine binding globulin (TBG), transthyretin (TTR), albumin or apolipoprotein B100. Cellular import and export of these charged, highly hydrophobic amino acid derivatives requires a number of cell-membrane transporters or facilitators such as MCT8 or MCT10 and members of the OATP and LAT families of transporters. Depending on their structure, the thyroid hormone metabolites exert their cellular action by binding and thus modulating the function of various receptors systems (e.g., ανβ3 integrin receptor and transient receptor potential channels (TR…
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Tetrac, a deaminated side chain metabolite of T4, present in human serum at concentrations similar to those of T3, antagonizes T4 (and also T3) actions at the integrin receptor signaling.
“The T4 metabolite Tetrac, a deaminated side chain metabolite, present in human serum at concentrations similar to those of T3 (3, 9) antagonizes such T4 (and also T3) actions at the integrin receptor signaling.”
From 3,5-T2—A Janus-Faced Thyroid Hormone Metabolite Exerts Both Canonical T3-Mimetic Endocrine and Intracrine Hepatic Action (2020) · cites this paper as [3]
Extrathyroidal formation of 3,5-T2 has been supported by studies using radioimmunoassays based on poly- or monoclonal antibodies.
“Most of these studies were feasible after the development of specific radioimmunoassays, based on poly- or monoclonal antibodies in the Seventies of the last century, and supported extrathyroidal formation of 3,5-T2, which had been previously demonstrated using radioisotope-labeled TH in humans, experimental animal models, and in vitro systems [see recent reviews: (3, 9)].”
From 3,5-T2—A Janus-Faced Thyroid Hormone Metabolite Exerts Both Canonical T3-Mimetic Endocrine and Intracrine Hepatic Action (2020) · cites this paper as [3]
L-T4 is solely produced by the thyroid gland and serves as a prohormone, while T3 is in part secreted by the thyroid gland and mainly generated in extra-thyroidal tissues by either type 1 or type 2 deiodinase (DIO1, DIO2).
“A century of thyroxine research has led to the commonly held opinion in the thyroid hormone community that 3,3′,5,5′-tetraiodo-L-thyronine (L-Thyroxine, L-T4), which is solely produced by the thyroid gland, serves as a prohormone while T3 (3,3′5-triiodo-L-thyronine), in part secreted by the thyroid gland, is mainly generated in various extra-thyroidal tissues by either type 1 or type 2 deiodinase”
From 3,5-T2—A Janus-Faced Thyroid Hormone Metabolite Exerts Both Canonical T3-Mimetic Endocrine and Intracrine Hepatic Action (2020) · cites this paper as [3]
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Chaker, L., Razvi, S., Bensenor, I. M., Azizi, F., Pearce, E. N., & Peeters, R. P. (2022) · Nature Reviews Disease Primers · doi:10.1038/s41572-022-00357-7 · Cited by 330 · see citing works
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Self-citation
- Authors
- Köhrle, J.
- Affiliations
- Freie Universität Berlin (DE)
- Corresponding author
- Köhrle, Josef
- ORCID
- Köhrle, Josef
- Venue
- Methods in Molecular Biology
- Publisher
- Springer New York
- Published
- 2018
- Volume
- 1801
- Pages
- 85-104
- ISSN
- 1064-3745 (ISSN-L)
- 1940-6029
- OpenAlex
- W2807780965
- Cited by
- 47
- References
- 9
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 5 · 2023: 4 · 2022: 12 · 2021: 5 · 2020: 9 · 2019: 9
- FWCI
- 33.56
- Type
- book chapter
- Language
- en
- Open access
- closed
- Locations
- Methods in molecular biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Chemical Analysis and Environmental Impact
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Keywords
- thyroid hormones, thyroid hormone metabolites, thyroxine, triiodothyronine, reverse T3, thyronamines, thyroid hormone binding proteins, thyroxine-binding globulin, prealbumin, apolipoprotein B-100, thyroid hormone transporters, MCT8, MCT10, organic anion transporting polypeptides, LAT, thyroid hormone receptor, deiodinases, sulfation, glucuronidation, hormone metabolism
- MeSH terms
- Animals, Circadian Rhythm, Energy Metabolism, Humans, Immunoassay, Iodide Peroxidase, Protein Binding, Receptors, Thyroid Hormone, Mass Spectrometry, Thyroid Gland, Thyroid Hormones, Thyronines, Protein Biosynthesis, Signal Transduction
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