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Life without Thyroxine to 3,5,3′-Triiodothyronine Conversion: Studies in Mice Devoid of the 5′-Deiodinases
Open accessAbstract
Considerable indirect evidence suggests that the type 2 deiodinase (D2) generates T(3) from T(4) for local use in specific tissues including pituitary, brown fat, and brain, whereas the type I deiodinase (D1) generates T(3) from T(4) in the thyroid and peripheral tissues primarily for export to plasma. From studies in deiodinase-deficient mice, the importance of the D2 for local T(3) generation has been confirmed. However, the phenotypes of these D1 knockout (KO) and D2KO mice are surprisingly mild and their serum T(3) level, general health, and reproductive capacity are unimpaired. To explore further the importance of 5'deiodination in thyroid hormone economy, we used a mouse devoid of both D1 and D2 activity. In general, the phenotype of the D1/D2KO mouse is the sum of the phenotypes of the D1KO and D2KO mice. It appears healthy and breeds well, and most surprisingly its serum T(3) level is normal. However, impairments in brain gene expression and possibly neurological function are somewhat greater than those seen in the D2KO mouse, and the serum rT(3) level is elevated 6-fold in the D1/D2KO mouse but only 2-fold in the D1KO mouse and not at all in the D2KO mouse. The data suggest that whereas D1 and D2 are not essential for the maintenance of the serum T(3) level, they do serve important roles in thyroid hormone homeostasis, the D2 being critical for local T(3) production and the D1 playing an important role in iodide conservation by serving as a scavenger enzyme in peripheral tissues and the thyroid.
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“The creation of genetically modified mice with inactivation of the deiodinase genes (mice that are not capable of extrathyroidal conversion of T4 to T3) led to the unexpected observation that in these mice the serum T3 levels remained normal, even in the absence of all deiodinases. Thyroid production of T3 is increased and the HPT axis tolerates elevated serum T4 and TSH levels to preserve serum T”
From Emerging Therapies in Hypothyroidism (2024) · cites this paper as [19]
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Metadata
- Authors
- Galton, V. A., Schneider, M. J., Clark, A. S., & St. Germain, D. L.
- Affiliations
- Departments of Physiology (V.A.G., M.J.S., D.L.S.G.), Dartmouth Medical School, Lebanon, New Hampshire 03756
- Dartmouth College (US)
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2009-02-05
- Volume
- 150
- Issue
- 6
- Pages
- 2957-2963
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC2689801
- OpenAlex
- W2109458276
- Cited by
- 181
- References
- 37
- Citations by year
- 2026: 1 · 2025: 10 · 2024: 4 · 2023: 8 · 2022: 9 · 2021: 6 · 2020: 10 · 2019: 11 · 2018: 8 · 2017: 13 · 2016: 12 · 2015: 9 · 2014: 19 · 2013: 6 · 2012: 11
- FWCI
- 13.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrinology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Dartmouth College
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK054716, DK-54716)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD09020, R01HD009020)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Keywords
- type 2 deiodinase, type I deiodinase, triiodothyronine, thyroxine, thyroid hormone homeostasis, reverse T3, brain gene expression
- MeSH terms
- Iodothyronine Deiodinase Type II, Animals, Brain, Homeostasis, Iodide Peroxidase, Iodine, Learning, Locomotion, Memory, Mice, Inbred C57BL, RNA, Messenger, Thyroid Gland, Thyrotropin, Thyroxine, Triiodothyronine, Mice, Knockout, Mice
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