Studies of the Hormonal Regulation of Type 2 5′-Iodothyronine Deiodinase Messenger Ribonucleic Acid in Pituitary Tumor Cells Using Semiquantitative Reverse Transcription-Polymerase Chain Reaction**This work was supported by NIH Grant DK-36256.
Abstract
We developed a sensitive competitive RT-PCR technique for quantitating the ratio of D2 to cyclophilin messenger RNA (mRNA) and used this to study type 2 deiodinase (D2) mRNA regulation. Hyperthyroidism in rats causes a 2- to 3-fold reduction in anterior pituitary and medial basal hypothalamus (MBH). Thyroid hormone (T3) withdrawal increased the D2/cyclophilin ratio 2- to 3-fold over 48 h in both GC and GH4C1 cells. T3 additional reduced D2 gene transcription by 50% over 2 h and about 30% over the next 2 h. D2 mRNA half-life is 2 h and is not affected by T3, indicating that its effect is due to suppression of D2 gene transcription. The T3 effect did not require new protein synthesis. Longer treatment with T3 led to a maximum decrease of 70% in D2 mRNA, indicating that there is also a T3-independent transcriptional component of the D2 gene. 3,3',5'-Triiodothyronine (reverse T3) caused a slight increase D2 mRNA over 24 h but an 80-90% decrease in D2 activity, indicating that it acts posttranscriptionally. Dexamethasone, 8 Br-cAMP, and TRH also caused modest increases in D2 mRNA in pituitary tumor cells. We conclude that D2 gene transcription has both T3-dependent and T3-independent components. Thus, posttranscriptional effects of D2 substrates such as T4 will be required for complete feedback inhibition of D2 activity. The short half-life of D2 mRNA and D2 protein explains the rapid response of D2 activity to thyroid hormone administration.
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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 [30]
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The type 2 iodothyronine deiodinase is expressed primarily in glial cells in the neonatal rat brain
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Type 2 iodothyronine deiodinase is highly expressed in human thyroid.
Salvatore, D., Tu, H., Harney, J. W., & Larsen, P. R. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118880 · Cited by 196 · see citing works
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Cellular and Molecular Basis of Deiodinase-Regulated Thyroid Hormone Signaling1
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Type 2 iodothyronine deiodinase is the major source of plasma T3 in euthyroid humans
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Paradigms of dynamic control of thyroid hormone signaling
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Thyroid Hormone Signaling and Homeostasis During Aging
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Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion
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Hypothyroidism induces type 2 iodothyronine deiodinase expression in mouse heart and testis
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- Authors
- Kim, S.-W., Harney, J. W., & Larsen, P. R.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Larsen, P. Reed
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 1998-12-01
- Volume
- 139
- Issue
- 12
- Pages
- 4895-4905
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W1977026615
- Cited by
- 86
- References
- 3
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 5 · 2022: 1 · 2021: 1 · 2019: 1 · 2018: 2 · 2016: 3 · 2015: 1 · 2014: 1 · 2013: 2 · 2012: 3
- FWCI
- 4.06
- 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 (DK36256, R01DK036256)
- 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, thyroid hormone regulation, mRNA regulation, cyclophilin, hyperthyroidism, thyroid hormone withdrawal, post-transcriptional regulation, mRNA half-life, reverse T3, dexamethasone, thyrotropin-releasing hormone, cyclic AMP, anterior pituitary, medial basal hypothalamus, pituitary tumor cells, GC cells, GH4C1 cells
- MeSH terms
- Animals, Dexamethasone, Hormones, Iodide Peroxidase, Isoenzymes, Male, Pituitary Neoplasms, RNA, Messenger, Thyrotropin-Releasing Hormone, Triiodothyronine, Triiodothyronine, Reverse, Tumor Cells, Cultured, 1-Methyl-3-isobutylxanthine, 8-Bromo Cyclic Adenosine Monophosphate, Blotting, Northern, Rats, Sprague-Dawley, Reverse Transcriptase Polymerase Chain Reaction, Rats
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