Expression and regulation of type II iodothyronine deiodinase in cultured human skeletal muscle cells
Abstract
T4, which is a major secretory product of the thyroid gland, needs to be converted to T3 by iodothyronine deiodinase to exert its biological activity. After the molecular cloning of human type II iodothyronine deiodinase (DII) complementary DNA, DII expression was unexpectedly detected in human skeletal muscle tissue. In the present study, we have identified DII activity and DII messenger ribonucleic acid (mRNA) in cultured human skeletal muscle cells and studied the mechanisms involved in the regulation of DII expression in those cells. All of the characteristics of the deiodinating activity in cultured human skeletal muscle cells were compatible with those of DII. Northern analysis has demonstrated that DII mRNA, approximately 7.5 kb in size, was expressed in cultured human skeletal muscle cells. DII mRNA and DII activity were rapidly increased by (Bu)2cAMP, forskolin, or beta-adrenergic agonists and were negatively regulated by thyroid hormones in cultured human skeletal muscle cells. Although interleukin-1beta and interleukin-6 did not decrease DII expression in cultured human skeletal muscle cells, tumor necrosis factor-alpha decreased DII expression in those cells in a dose-dependent manner. These data have demonstrated, for the first time, that DII activity and DII mRNA are present in cultured human skeletal muscle cells, and that the DII expression is stimulated by beta-adrenergic mechanisms through a cAMP-mediated pathway and is negatively regulated by thyroid hormones and tumor necrosis factor-alpha.
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T3 represses gene transcription of DIO2, forming a negative feedback loop to keep intracellular T3 within a range.
“T3 can repress the gene transcription of DIO2, the primary activating enzyme that converts T4 into T3, therefore forming a negative feedback loop to keep intracellular T3 within a range (30–32).”
From Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion (2022) · cites this paper as [31]
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Type 2 iodothyronine deiodinase is highly expressed in human thyroid.
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Type 2 iodothyronine deiodinase is the major source of plasma T3 in euthyroid humans
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- Authors
- Hosoi, Y.
- Affiliations
- Gunma University (JP)
- Venue
- Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1999-09-01
- Volume
- 84
- Issue
- 9
- Pages
- 3293-3300
- ISSN
- 0021-972X (ISSN-L)
- OpenAlex
- W2164730238
- Cited by
- 80
- References
- 1
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 4 · 2016: 2 · 2015: 3 · 2014: 2 · 2013: 5 · 2012: 3
- FWCI
- 2.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- type 2 deiodinase, skeletal muscle cells, T4 to T3 conversion, thyroid hormone regulation, beta-adrenergic stimulation, cAMP signaling, forskolin, TNF-α, IL-1β, interleukin-6, gene expression regulation
- MeSH terms
- Adrenergic beta-Agonists, Cells, Cultured, Bucladesine, Colforsin, Humans, Iodide Peroxidase, Isoproterenol, Norepinephrine, RNA, Messenger, Thyroid Hormones, Tumor Necrosis Factor-alpha, Blotting, Northern, Gene Expression Regulation, Enzymologic, Muscle, Skeletal
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