Propylthiouracil inhibits the conversion of l-thyroxine to l-triiodothyronine

Oppenheimer, Jack H.; Schwartz, Harold L.; Surks, Martin I.

doi:10.1172/jci107063

Cited by 258Thyroid Disorders and TreatmentsChemical Analysis and Environmental ImpactThyroid Cancer Diagnosis and Treatment

Propylthiouracil inhibits the conversion of l-thyroxine to l-triiodothyronine

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Oppenheimer, Jack H., Schwartz, Harold L., Surks, Martin I.·1972·Journal of Clinical Investigation

DOI 10.1172/jci107063PMC PMC292418

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Abstract

6-n-propylthiouracil (PTU) administered to male Sprague-Dawley rats maintained on 2 and 5 mug L-thyroxine (T(4))/100 g body weight resulted in a marked reduction in the rate of conversion of L-thyroxine to L-triiodothyronine (T(3)). These effects could not be ascribed to induced hypothyroidism since the group maintained on 5 mug T(4)/day had normal levels of liver mitochondrial alpha glycerophosphate dehydrogenase. In confirmation of previous studies, PTU also reduced the fractional rate of deiodination of T(3). These observations provide a possible explanation of the many published observations indicating that PTU antagonizes the tissue effects of T(4) but not of T(3). The data suggest that monodeiodination of T(4) but not of T(3) is essential before hormonal effects can be manifested at the cellular level.

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Propylthiouracil (PTU) inhibits D1, explaining some of its therapeutic benefit in this setting.
“Propylthiouracil (PTU) inhibits D1, explaining some of its therapeutic benefit in this setting (14).”
From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [14]
The Results report that PTU markedly reduced conversion of T4 to T3 in rats, and the Introduction links reduced conversion to weaker T4 effects. But the Discussion says the site of inhibition was unknown; the paper does not identify D1 or establish a therapeutic benefit in the citing sentence’s setting. Page numbers were not available in our copy. (LLM, conf=0.88)
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Oppenheimer, J. H., D. Koerner, H. L. Schwartz, and M. I. Surks. Specific nuclear triiodothyronine binding sites in rat liver and kidney. J. Clin. Endocrinol. Metab. In press.

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CONCISE PUBLICATIONS Propylthiouracil Inhibits the Conversion of L-Thyroxine to L-Triiodothyronine AN EXPLANATION OF THE ANTITHYROXINE EFFECT OF PROPYLTHIOURACIL AND EVIDENCE SUPPORTING THE CONCEPT THAT TRIIODOTHYRONINE IS THE ACTIVE THYROID HORMONE
Oppenheimer, J. H., Sahwariz, H. L., & Surks, M. I. (1972)
Self-citation
AN EXPLANATION OF THE ANTITHYROXINE EFFECT OF PROPYLTHIOURACIL AND EVIDENCE SUPPORTING THE CONCEPT THAT TRIIODOTHYRONINE IS THE ACTIVE THYROID HORMONE
Oppenheimer, J. H., & Surks, M. I. (1972) · Cited by 9 · see citing works
Self-citation
Evidence for Two Tissue-specific Pathways for In Vivo Thyroxine 5′-Deiodination in the Rat
Silva, J. E., Leonard, J. L., Crantz, F. R., & Larsen, P. R. (1982) · Journal of Clinical Investigation · doi:10.1172/jci110554 · Cited by 143 · see citing works
Inhibition of peripheral deiodination of 3,5,3′-triiodothyronine: an adverse effect of propylthiouracil in the treatment of T3-thyrotoxicosis
Heinen, E., Herrmann, J., Mosny, D., Moreno, F. S., Teschke, R., & Krüskemper, H. L. (1981) · Journal of Endocrinological Investigation · doi:10.1007/bf03349453 · Cited by 6 · see citing works
INHIBITION BY PROPYLTHIOURACIL OF THE EXTRATHYROIDAL FORMATION OF TRIIODOTHYRONINE FROM THYROXINE
Bernal, J., & del Rey, F. E. (1974) · European Journal of Endocrinology · doi:10.1530/acta.0.0770276 · Cited by 16 · see citing works

Authors: Oppenheimer, J. H., Schwartz, H. L., & Surks, M. I.
Affiliations: Albert Einstein College of Medicine (US)
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 1972-09-01
Volume: 51
Issue: 9
Pages: 2493-2497
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci107063
PMC: PMC292418
OpenAlex: W1758817371
Cited by: 258
References: 36
Citations by year: 2024: 3 · 2023: 2 · 2022: 5 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 4 · 2013: 2 · 2012: 6
FWCI: 16.77
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Health Research Council of the City of New York
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: propylthiouracil, levothyroxine, triiodothyronine, T4 to T3 conversion, deiodination, thyroid hormone antagonism, alpha-glycerophosphate dehydrogenase, liver mitochondria, hypothyroidism
MeSH terms: Administration, Oral, Animals, Chromatography, Paper, Chromatography, Thin Layer, Glucosephosphate Dehydrogenase, Injections, Subcutaneous, Iodine Radioisotopes, Male, Mitochondria, Liver, Propylthiouracil, Thyroidectomy, Thyroxine, Triiodothyronine, Rats

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Propylthiouracil inhibits the conversion of l-thyroxine to l-triiodothyronine

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