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The Contribution of Local Tissue Thyroxine Monodeiodination to the Nuclear 3,5,3′- Triiodothyronine in Pituitary, Liver, and Kidney of Euthyroid Rats*
Abstract
The contributions of local T4 monodeiodination and plasma T3 to the nuclear T3 of anterior pituitary, liver, and kidney were measured in euthyroid rats. After injection of [125I]T4, there was a gradual increase in the quantity of plasma [125I]T3 in excess of injected contaminant, which peaked at approximately 12 h after injection and remained a constant fraction of plasma [125I]T4 (2.8 X 10(-3) after that time. In the nuclei of anterior pituitary tissue, there was also a slow increase in locally produced [125I]T3 (in excess of that which could be accounted for by plasma [125I]T3) which appeared to peak at about 16 h after [125I]T4 administration. The ratio of nuclear [125I]T3 generated intracellularly to plasma [125I]T4 was constant at 18 and 24 h after T4 injection and was 13 +/- 2 X 10(-3) in nuclei of pituitary, 2.0 +/- 0.4 x 10(-3) in liver, and 0.47 +/- 0.1 x 10(-3) in kidney (all values are mean +/- SD). This locally generated T3 resulted in a markedly higher nuclear to plasma (N:P) ratio for [125I]T3 than for injected [131I]T3 in the same animals. The N:P ratio for [125I]T3 at equilibrium after injected T4 was 2.4 +/- 0.6, 0.47 +/- 0.09, and 0.10 +/- 0.03 (nanograms of T3 (mg DNA)-1/ng T3 ml-1) in pituitary, liver, and kidney. Comparable values for [131I]T3 N:P ratios were 0.47 +/- 0.14 (pituitary), 0.18 +/- 0.01 (liver), and 0.036 +/- 0.008 (kidney). Using RIA values for plasma T4 and T3 concentrations in these rats and maximal nuclear T3-binding capacities estimated in parallel experiments, the gravimetric quantities of nuclear T3 derived from plasma T3 and from local T4 to T3 monodeiodination were estimated and expressed as the percentage of saturation of T3 receptors. Seventy-eight percent of nuclear T3 receptor sites in anterior pituitary were occupied with one-half of the nuclear T3 derived directly from plasma T3 and the other half from intrapituitary T4 monodeiodination. Local T4 monodeiodination provided only 28% and 14%, respectively, of the nuclear T3 in liver and kidney, and the nuclear receptors of these tissues were about 50% saturated. Since our previous studies have shown that the occupancy of the pituitary nuclear T3 receptors may regulate TSH release, these data provide a mechanism by which TSH secretion could be altered by changes in either plasma T3 or T4, whereas nuclear T3 in liver and kidney is predominantly a function of the plasma T3 concentration.
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“Expressed in the endoplasmic reticulum (21,22), D2 generated T3 first accumulates in the cell long enough to contribute to the nuclear T 3 pool (23); thus, changes in D2 activity can cause intracrine tissue-specific changes in thyroid signaling.”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [23]
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Metadata
- Authors
- SILVA, J. E., DICK, T. E., & LARSEN, P. R.
- Affiliations
- Harvard University (US)
- ORCID
- DICK, T. E.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 1978-10
- Volume
- 103
- Issue
- 4
- Pages
- 1196-1207
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2021534182
- Cited by
- 189
- References
- 25
- Citations by year
- 2022: 3 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 4 · 2015: 3 · 2014: 4 · 2013: 1 · 2012: 3
- FWCI
- 10.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Chemical Analysis and Environmental Impact
- Keywords
- thyroid hormone deiodination, T4 to T3 conversion, anterior pituitary, liver, kidney, thyroid hormone metabolism
- MeSH terms
- Animals, Cell Nucleus, Kidney, Liver, Male, Mathematics, Pituitary Gland, Anterior, Receptors, Cell Surface, Thyroxine, Triiodothyronine, Rats
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