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Local impact of thyroid hormone inactivation
Open accessAbstract
Deiodination is a critical process by which the minimally active thyroxine (T(4)) molecule is converted into the favorite ligand for thyroid hormone (TH) receptors, triiodothyronine (T(3)). The iodothyronine deiodinases type 1, 2, and 3 (D1, D2, and D3) constitute a potent mechanism of TH activation (D1 and D2) or inactivation (D3), which functions by tissue specifically regulating TH bioavailability. D2 and D3 are widely expressed and in a dynamically and tightly coordinated fashion, thereby allowing cells to customize their own TH activity. D3, the major T(3) and T(4) inactivating deiodinase, catalyzes their conversion to 3,3'-diiodothyronine and to reverse T(3) respectively. According to common wisdom, D3 plays a major role in lowering serum TH concentrations during development, as supported by the much wider D3 tissue expression in the embryo structures than in the adult tissues. However, several recent studies show that D3 is reexpressed in adult life in various pathophysiological contexts, which strengthens the concept that cell-specific TH inactivation is a critical mediator in cellular TH metabolism. This review focuses on the progress made in understanding the physiological function and significance of D3. It summarizes the intriguing evidence that D3 plays a pivotal role in defining local TH concentration in the developing fetus and in several conditions in adult life.
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“In these critical conditions, where a reduction of the metabolism and a reduced T3 level is physiologically desirable, the conversion of T4 to T3 is reduced, while the conversion to rT3 is increased.”
From Can Reverse T3 Assay Be Employed to Guide T4 vs. T4/T3 Therapy in Hypothyroidism? (2019) · cites this paper as [5]
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“Due to alterations in rates of local deiodination in tissues, thyroid hormone signaling can change irrespective of serum hormonal concentrations (3, 5).”
From Can Reverse T3 Assay Be Employed to Guide T4 vs. T4/T3 Therapy in Hypothyroidism? (2019) · cites this paper as [5]
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Metadata
- Authors
- Dentice, M., & Salvatore, D.
- Affiliations
- Federico II University Hospital (IT)
- Corresponding author
- Dentice, Monica
- Venue
- Journal of Endocrinology
- Publisher
- Bioscientifica
- Published
- 2011-03-11
- Volume
- 209
- Issue
- 3
- Pages
- 273-282
- ISSN
- 0022-0795 (ISSN-L)
- 1479-6805
- OpenAlex
- W2318017892
- Cited by
- 143
- References
- 94
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 9 · 2023: 5 · 2022: 4 · 2021: 11 · 2020: 8 · 2019: 11 · 2018: 11 · 2017: 16 · 2016: 6 · 2015: 8 · 2014: 8 · 2013: 14 · 2012: 13
- FWCI
- 1.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Funders
- Associazione Italiana per la Ricerca sul Cancro
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- thyroid hormone inactivation, triiodothyronine, thyroxine, thyroid hormone receptor, reverse T3, 3,3'-diiodothyronine, fetal thyroid development
- MeSH terms
- Aging, Animals, Humans, Iodide Peroxidase, Thyroid Hormones, Thyroxine, Triiodothyronine
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