The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Type 2 iodothyronine deiodinase is highly expressed in human thyroid.
Open accessAbstract
Type 2 iodothyronine deiodinase (D2) is a recently cloned selenodeiodinase thought to provide intracellular 3,5,3' triiodothyronine (T3) to a restricted group of tissues. We report here the presence of D2 mRNA in human thyroid at levels 50-150-fold higher than in placenta. Surprisingly, while type 1 deiodinase (D1) is known to be present in human thyroid, D2 has not been evaluated previously. D2 mRNA was especially high in thyroids from Graves' patients and in follicular adenomas. Stimulated thyroids had higher D2 to D1 mRNA ratios than normal or multinodular glands suggesting differential regulation of D1 and D2 expression. Microsomes from normal, Graves', and TSH-stimulated thyroids contained low Km D2 activity resistant to propylthiouracil (1 mM) or to inactivation by N-bromoacetyl T3, agents which block or inactivate D1. At 2 nM thyroxine (T4), 100 times the physiological-free T4 levels, 60-80% of T4 to T3 conversion in stimulated, but only 27% of that in normal thyroids, is catalyzed by D2. We conclude that intrathyroidal T4 to T3 conversion by D2 may contribute significantly to the relative increase in thyroidal T3 production in patients with Graves' disease, toxic adenomas, and, perhaps, iodine deficiency.
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“D2 activity in humans has been detected in various tissues, predominantly in the central nervous system, pituitary gland, thyroid, heart, brown adipose tissue, and skeletal muscle (1517).”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [16]
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“TSHR-mediated upregulation of DIO2 contributes significantly to the relative increase in intrathyroidal T4-to-T3 conversion and thus T3 production and higher circulating T3/T4 ratio in patients with Graves’ disease and toxic adenomas (182, 183).”
From Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion (2022) · cites this paper as [182]
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Citations
Cites
Current protocols in molecular biology
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Type I iodothyronine deiodinase is a selenocysteine-containing enzyme
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Self-citationAdrenergic activation of triiodothyronine production in brown adipose tissue
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Self-citationMolecular biological and biochemical characterization of the human type 2 selenodeiodinase.
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Self-citationKinetic evidence suggesting two mechanisms for iodothyronine 5'-deiodination in rat cerebral cortex.
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Self-citationCloning of a cDNA for the Type II Iodothyronine Deiodinase
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Self-citationNutritional and Hormonal Regulation of Thyroid Hormone Deiodinases
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Thyroid Hormone Regulates Type I Deiodinase Messenger RNA in Rat Liver
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Self-citationCloning and in vitro expression of the human selenoprotein, type I iodothyronine deiodinase
Mandel, S. J., Berry, M. J., Kieffer, J. D., Harney, J. W., Warne, R. L., & Larsen, P. R. (1992) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.75.4.1400883 · Cited by 114
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Leonard, J. L., Silva, J. E., Kaplan, M. M., MELLEN, S. A., Visser, T. J., & Larsen, P. R. (1984) · Endocrinology · doi:10.1210/endo-114-3-998 · Cited by 111
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Self-citationTriiodothyronine, Thyroxine, and Iodine in Purified Thyroglobulin from Patients with Graves' Disease
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Self-citationLoPresti, J. S., Eigen, A., Kaptein, E., Anderson, K. P., Spencer, C. A., & Nicoloff, J. T. (1989) · Journal of Clinical Investigation · doi:10.1172/jci114343 · Cited by 80
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Self-citationToyoda, N., Harney, J. W., Berry, M. J., & Larsen, P. R. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)31995-6 · Cited by 59
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Comparison of Kidney and Brown Adipose Tissue Iodothyronine 5′-Deiodinases*
Silva, J. E., MELLEN, S. A., & Larsen, P. R. (1987) · Endocrinology · doi:10.1210/endo-121-2-650 · Cited by 29
Self-citationThyroxine 5′-Deiodinase in Human Anterior Pituitary Tumors*
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Self-citationPhorbol esters, protein kinase C, and thyroxine 5'-deiodinase in brown adipocytes
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Self-citationEffect of thyroid status on catecholamine stimulation of thyroxine 5'-deiodinase in brown adipocytes
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Self-citation
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Cited by
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Jonklaas, J., Bianco, A. C., Bauer, A. J., Burman, K. D., Cappola, A. R., Celi, F. S., Cooper, D. S., Kim, B. W., Peeters, R. P., Rosenthal, M. S., et al. (2014) · Thyroid® · doi:10.1089/thy.2014.0028 · Cited by 1,928
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Self-citationCellular and Molecular Basis of Deiodinase-Regulated Thyroid Hormone Signaling1
Gereben, B., Zavacki, A. M., Ribich, S., Kim, B. W., Huang, S. A., Simonides, W. S., Zeöld, A., & Bianco, A. C. (2008) · Endocrine Reviews · doi:10.1210/er.2008-0019 · Cited by 891
Selenium, the Thyroid, and the Endocrine System
Köhrle, J., Jakob, F. J., Contempré, B., & Dumont, J. E. (2005) · Endocrine Reviews · doi:10.1210/er.2001-0034 · Cited by 535
Zimmermann, M. B., & Köhrle, J. (2002) · Thyroid · doi:10.1089/105072502761016494 · Cited by 352
Metadata
- Authors
- Salvatore, D., Tu, H., Harney, J. W., & Larsen, P. R.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Larsen, P R
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 1996-08-15
- Volume
- 98
- Issue
- 4
- Pages
- 962-968
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC507511
- OpenAlex
- W2011717087
- Cited by
- 196
- References
- 42
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 4 · 2022: 4 · 2021: 3 · 2020: 6 · 2019: 3 · 2018: 5 · 2017: 3 · 2016: 6 · 2015: 4 · 2014: 5 · 2013: 3 · 2012: 6
- FWCI
- 7.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK36256, 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 › Nursing › Nutrition and Dietetics › Selenium in Biological Systems
- Keywords
- type 2 deiodinase, type 1 iodothyronine deiodinase, thyroid gland, triiodothyronine, T4 to T3 conversion, Graves' disease, follicular adenoma, multinodular goiter, TSH stimulation, propylthiouracil, iodine deficiency, thyroid hormone metabolism
- MeSH terms
- Enzyme Inhibitors, Humans, Iodide Peroxidase, Isoenzymes, Kinetics, Microsomes, Placenta, Propylthiouracil, RNA, Messenger, Thyroid Gland, Thyroxine, Triiodothyronine, Gene Expression
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