Escape from the Acute Wolff-Chaikoff Effect Is Associated with a Decrease in Thyroid Sodium/Iodide Symporter Messenger Ribonucleic Acid and Protein1
Abstract
In 1948, Wolff and Chaikoff reported that organic binding of iodide in the thyroid was decreased when plasma iodide levels were elevated (acute Wolff-Chaikoff effect), and that adaptation or escape from the acute effect occurred in approximately 2 days, in the presence of continued high plasma iodide concentrations. We later demonstrated that the escape is attributable to a decrease in iodide transport into the thyroid, lowering the intrathyroidal iodine content below a critical inhibitory threshold and allowing organification of iodide to resume. We have now measured the rat thyroid sodium/iodide symporter (NIS) messenger RNA (mRNA) and protein levels, in response to both chronic and acute iodide excess, in an attempt to determine the mechanism responsible for the decreased iodide transport. Rats were given 0.05% NaI in their drinking water for 1 and 6 days in the chronic experiments, and a single 2000-microg dose of NaI i.p. in the acute experiments. Serum was collected for iodine and hormone measurements, and thyroids were frozen for subsequent measurement of NIS, TSH receptor, thyroid peroxidase (TPO), thyroglobulin, and cyclophilin mRNAs (by Northern blotting) as well as NIS protein (by Western blotting). Serum T4 and T3 concentrations were significantly decreased at 1 day in the chronic experiments and returned to normal at 6 days, and were unchanged in the acute experiments. Serum TSH levels were unchanged in both paradigms. Both NIS mRNA and protein were decreased at…
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High iodide downregulates NIS through inhibition of NIS transcription, shortening of NIS mRNA poly(A) tail and destabilization, and shortening of NIS protein half-life.
“NIS is downregulated by high iodide through several mechanisms. First of all, high iodide inhibits the transcription of NIS (216, 234, 235).”
From Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion (2022) · cites this paper as [216]
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Wartofsky, L., Ransii, B. J., & Ingbar, S. H. (1970) · Journal of Clinical Investigation · doi:10.1172/jci106225 · Cited by 141 · see citing works
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- Authors
- Eng, P. H. K., Cardona, G. R., Fang, S.-L., Previti, M., Alex, S., Carrasco, N., Chin, W. W., & Braverman, L. E.
- Affiliations
- Brigham and Women's Hospital (US)
- Albert Einstein College of Medicine (US)
- Corresponding author
- Eng, Peter H. K.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 1999-08
- Volume
- 140
- Issue
- 8
- Pages
- 3404-3410
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2002518487
- Cited by
- 418
- References
- 1
- Citations by year
- 2026: 12 · 2025: 13 · 2024: 16 · 2023: 16 · 2022: 18 · 2021: 15 · 2020: 18 · 2019: 22 · 2018: 19 · 2017: 18 · 2016: 17 · 2015: 18 · 2014: 24 · 2013: 17 · 2012: 21
- FWCI
- 6.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK18919, R01DK018919)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Chemical Analysis and Environmental Impact
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Keywords
- Wolff-Chaikoff effect, sodium iodide symporter, iodide excess, iodide transport, thyroid gland, thyroid peroxidase, Hashimoto's thyroiditis, transcriptional regulation, thyroglobulin, TSH receptor, cyclophilin, thyroid hormone synthesis, rat thyroid, thyroxine, triiodothyronine
- MeSH terms
- Sodium-Iodide Symporters, Animals, Carrier Proteins, Gene Expression Regulation, Iodide Peroxidase, Iodides, Iodine, Male, Membrane Proteins, RNA, Messenger, Sodium Iodide, Thyroglobulin, Thyroid Gland, Transcription, Genetic, Protein Biosynthesis, Water Supply, Rats, Sprague-Dawley, Peptidylprolyl Isomerase, Symporters, Rats
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