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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Cites
Current protocols in molecular biology
(1988) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(88)90131-4 · Cited by 4,234
Type I iodothyronine deiodinase is a selenocysteine-containing enzyme
Berry, M. J., Banu, L., & Larsen, P. R. (1991) · Nature · doi:10.1038/349438a0 · Cited by 883
Self-citationJh, M. (1964) · Annals of Internal Medicine · doi:10.7326/0003-4819-60-4-742_2 · Cited by 690
Larsen, P. R., Silva, J. E., & Kaplan, M. M. (1981) · Endocrine Reviews · doi:10.1210/edrv-2-1-87 · Cited by 546
Self-citationDumont, J. E., Lamy, F., Roger, P. P., & Maenhaut, C. (1992) · Physiological Reviews · doi:10.1152/physrev.1992.72.3.667 · Cited by 519
Berry, M. J., Banu, L., Harney, J. W., & Larsen, P. R. (1993) · The EMBO Journal · doi:10.1002/j.1460-2075.1993.tb06001.x · Cited by 428
Self-citationAdrenergic activation of triiodothyronine production in brown adipose tissue
Silva, J. E., & Larsen, P. R. (1983) · Nature · doi:10.1038/305712a0 · Cited by 401
Self-citationMolecular biological and biochemical characterization of the human type 2 selenodeiodinase.
Salvatore, D., Bartha, T., Harney, J. W., & Larsen, P. R. (1996) · Endocrinology · doi:10.1210/endo.137.8.8754756 · Cited by 284
Self-citationKinetic evidence suggesting two mechanisms for iodothyronine 5'-deiodination in rat cerebral cortex.
Visser, T. J., Leonard, J. L., Kaplan, M. M., & Larsen, P. R. (1982) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.79.16.5080 · Cited by 234
Self-citationSilva, J. E., & Larsen, P. R. (1985) · Journal of Clinical Investigation · doi:10.1172/jci112239 · Cited by 207
Self-citation
Research works printed but not linked: 1
- Larsen, P.R., and SH. Ingbar. 1992. The thyroid. In Textbook of Endo- crinology. J.D. Wilson and D.W. Foster, editors. W.B. Saunders, Co., Philadel- phia. 357-487.
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
Bianco, A. C., Salvatore, D., Gereben, B., Berry, M. J., & Larsen, P. R. (2002) · Endocrine Reviews · doi:10.1210/edrv.23.1.0455 · Cited by 1,853
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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