Type 2 iodothyronine deiodinase is the major source of plasma T3 in euthyroid humans
Open accessAbstract
The relative roles of the types 1 and 2 iodothyronine deiodinases (D1 and D2) in extrathyroidal 3,5,3'-triiodothyronine (T3) production in humans are unknown. We calculated the rate of thyroxine (T4) to T3 conversion by intact cells transiently expressing D1 or D2 at low (2 pM), normal (20 pM), and high (200 pM) free T4 concentrations. Deiodinase activities were then assayed in cell sonicates. The ratio of T3 production in cell sonicates (catalytic efficiency) was multiplied by the tissue activities reported in human liver (D1) and skeletal muscle (D2). From these calculations, we predict that in euthyroid humans, D2-generated T3 is 29 nmol/d, while that of D1-generated T3 is 15 nmol/d, from these major deiodinase-expressing tissues. The total estimated extrathyroidal T3 production, 44 nmol/d, is in close agreement with the 40 nmol T3/d based on previous kinetic studies. D2-generated T3 production accounts for approximately 71% of the peripheral T3 production in hypothyroidism, but D1 for approximately 67% in thyrotoxic patients. We also show that the intracellular D2-generated T3 has a greater effect on T3-dependent gene transcription than that from D1, which indicates that generation of nuclear T3 is an intrinsic property of the D2 protein. We suggest that impairment of D2-generated T3 is the major cause of the reduced T3 production in the euthyroid sick syndrome.
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In muscle, local conversion of T4 to T3 by DIO2 is important for muscle function both in rodents and in humans.
“In muscle, local conversion of T4 toT3 by DIO2 is important for muscle function both in rodents and in humans [4, 26, 27].”
From An update on non-thyroidal illness syndrome (2021) · cites this paper as [26]
The section “D2-generated T3 in human skeletal muscle” (page not provided) shows that human skeletal muscle cells convert T4 to T3 through D2. It does not establish that this conversion is important for muscle function, and the cited passages provide no rodent muscle-function finding. (LLM, conf=0.86)
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References 41 · Cited by 360
- Authors
- Luiza Maia, A.
- Venue
- Journal of Clinical Investigation
- Published
- 2005-08-25
- Volume
- 115
- Issue
- 9
- Pages
- 2524-2533
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC1190373
- OpenAlex
- W2098101263
- Cited by
- 360
- References
- 41
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 11 · 2023: 11 · 2022: 17 · 2021: 17 · 2020: 15 · 2019: 15 · 2018: 13 · 2017: 17 · 2016: 22 · 2015: 17 · 2014: 19 · 2013: 8 · 2012: 16
- FWCI
- 13.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 064643, DK060494, DK36256, K08DK064643, K08DK060494, R01DK036256, T32DK007529, DK-07529)
- 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
- type 2 deiodinase, type 1 iodothyronine deiodinase, T4 to T3 conversion, low T3 syndrome, liver, skeletal muscle, hypothyroidism, thyrotoxicosis, catalytic efficiency
- MeSH terms
- Iodothyronine Deiodinase Type II, Cell Line, Humans, Iodide Peroxidase, Iodine Radioisotopes, Liver, Thyroid Gland, Thyroxine, Triiodothyronine, Molecular Structure, Muscle, Skeletal
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