Targeted Disruption of the Type 1 Selenodeiodinase Gene (Dio1) Results in Marked Changes in Thyroid Hormone Economy in Mice
Abstract
The type 1 deiodinase (D1) is thought to be an important source of T3 in the euthyroid state. To explore the role of the D1 in thyroid hormone economy, a D1-deficient mouse (D1KO) was made by targeted disruption of the Dio1 gene. The general health and reproductive capacity of the D1KO mouse were seemingly unimpaired. In serum, levels of T4 and rT3 were elevated, whereas those of TSH and T3 were unchanged, as were several indices of peripheral thyroid status. It thus appears that the D1 is not essential for the maintenance of a normal serum T3 level in euthyroid mice. However, D1 deficiency resulted in marked changes in the metabolism and excretion of iodothyronines. Fecal excretion of endogenous iodothyronines was greatly increased. Furthermore, when compared with both wild-type and D2-deficient mice, fecal excretion of [125I]iodothyronines was greatly increased in D1KO mice during the 48 h after injection of [125I]T4 or [125I]T3, whereas urinary excretion of [125I]iodide was markedly diminished. From these data it was estimated that a majority of the iodide generated by the D1 was derived from substrates other than T4. Treatment with T3 resulted in a significantly higher serum T3 level and a greater degree of hyperthyroidism in D1KO mice than in wild-type mice. We conclude that, although the D1 is of questionable importance to the wellbeing of the euthyroid mouse, it may play a major role in limiting the detrimental effects of conditions that alter normal thyroid function, including hyperthyroidism and iodine deficiency.
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D1 produces a small amount of circulating T3 (estimated approximately 24% in healthy individuals) and preserves iodide by removing iodine from inactive metabolites of T3 and T4 in the liver and kidney.
“D1 has a dual role, both producing a small amount of circulating T3 (D1 is estimated to contribute approximately 24% of circulating T3 in healthy individuals) and also preserving iodide by removing iodine from inactive metabolites of T3 and T4 in the liver and kidney (conjugated iodothyronines) (13).”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [13]
The Discussion (page unavailable) supports two D1 activities: conversion of T4 to T3 and release of iodide from inactive T3 and T4 metabolites, including sulfate conjugates. The paper studies mice and does not give the claimed 24% estimate for healthy individuals. Its excretion results show iodide release, but do not establish that this process preserves iodide. (LLM, conf=0.87)
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- Authors
- Schneider, M. J., Fiering, S. N., Thai, B., Wu, S.-Y., St. Germain, E., Parlow, A. F., St. Germain, D. L., & Galton, V. A.
- Affiliations
- Departments of Physiology, Microbiology, and Medicine (M.J.S., S.N.F., E.S.G., D.L.S.G., V.A.G.), Dartmouth Medical School, Lebanon, New Hampshire 03756
- United States Department of Veterans Affairs (US)
- Harbor–UCLA Medical Center (US)
- Corresponding author
- Galton, Valerie Anne
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2006-01-01
- Volume
- 147
- Issue
- 1
- Pages
- 580-589
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2105299400
- Cited by
- 265
- References
- 35
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 9 · 2023: 6 · 2022: 15 · 2021: 14 · 2020: 10 · 2019: 15 · 2018: 10 · 2017: 10 · 2016: 14 · 2015: 15 · 2014: 19 · 2013: 15 · 2012: 13
- FWCI
- 6.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Dartmouth College
- U.S. Public Health Service
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK042271, DK-42271)
- 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 › Thyroid Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- type I deiodinase, DIO1, thyroxine, reverse T3, urinary iodide excretion, hyperthyroidism, iodine deficiency, thyroid hormone metabolism, knockout mice
- MeSH terms
- Animals, Base Sequence, Codon, Exons, Iodide Peroxidase, RNA, Messenger, Thyroid Gland, Thyroxine, Triiodothyronine, Restriction Mapping, Selenocysteine, Gene Deletion, DNA Primers, Mice, Knockout, Mice
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