Propylthiouracil blocks extrathyroidal conversion of thyroxine to triiodothyronine and augments thyrotropin secretion in man.

Geffner, David L.; Azukizawa, M; Hershman, Jerome M.

doi:10.1172/jci107925

Cited by 188 publications

(86 citation statements)

References 30 publications

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“…This is in accordance with previous findings that administration of propylthiouracil to rats (Oppenheimer et al, 1972), as well as to humans (Saberi et al, 1975;Geffner et al, 1975), blocks the extrathyroidal production of tri-iodothyronine. Our data indicate that propylthiouracil decreases markedly the production from thyroxine of both tri-iodothyronine and reverse tri-iodothyronine (as indicated for the latter by the fall in the generation of di-iodothyronine).…”

Section: Resultssupporting

confidence: 93%

Sequential deiodination of thyroxine in rat liver homogenate

Visser¹,

Fekkes²,

Docter³

et al. 1978

Biochemical Journal

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Rat liver homogenate was incubated at 37°C with thyroxine, 3,3',5-tri-iodothyronine, 3,3',5'-tri-iodothyronine or 3,3'-di-iodothyronine. The degradation or accumulation of these compounds was measured by specific radioimmunoassays. (1) Production of 3,3',5-tri-iodothyronine from thyroxine was highest at pH 6.0-6.5 and was markedly stimulated by the addition of dithiothreitol and effectively inhibited in the presence of 6-propyl-2-thiouracil. (2) Accumulation of 3,3',5'-tri-iodothyronine on incubation of thyroxine with homogenate was only observed above pH 8.5. Otherwise the product was converted into 3,3'-di-iodothyronine too rapidly to allow its measurement. By measuring 3,3'-di-iodothyronine it was deduced that 5-deiodination of thyroxine was most effective at approx. pH 8.0. Dithiothreitol powerfully stimulated this reaction and 6-propyl-2-thiouracil strongly inhibited. (3) Monodeiodination of the tyrosine ring of 3,3',5-tri-iodothyronine was the slowest reaction, was optimal at pH 8.0 and was less affected by dithiothreitol and 6-propyl-2-thiouracil than the above reactions. (4) 5'-

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Section: Resultssupporting

confidence: 93%

Sequential deiodination of thyroxine in rat liver homogenate

Visser¹,

Fekkes²,

Docter³

et al. 1978

Biochemical Journal

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“…Reverse T3 (rT3) was infused subcutaneously (25 nmol·100 g body weight p<0.05 at least vs the hypothyroid leptin-treated group feeding conditions. Such effects of PTU on thyroid hormones were similar to those reported in humans [39,40]. The state of hypothyroidism induced by PTU was also documented by the observation of a marked decrease in the mRNA expression of liver D1 (51.1±4.7 arbitrary units in hypothyroid pair-fed rats vs 100.0±14.2 arbitrary units in euthyroid pair-fed rats, p<0.001).…”

Section: As Depicted Insupporting

confidence: 85%

Hypothyroidism in rats decreases peripheral glucose utilisation, a defect partially corrected by central leptin infusion

et al. 2005

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Aims/hypothesis: The aims of this work were to determine the effect of hypothyroidism on insulin-stimulated glucose turnover and to unravel the potential mechanisms involved in such an effect. Methods: Hypothyroidism was induced by administration of propylthiouracil, with partial T4 substitution. Euglycaemic-hyperinsulinaemic clamps, associated with the labelled 2-deoxy-D-glucose technique for measuring tissue-specific glucose utilisation, were used. To assess a possible involvement of leptin in the modulation of glucose metabolism by hypothyroidism, leptin was infused intracerebroventricularly for 6 days. A group of leptin-infused rats was treated with rT3 to determine a potential role of T3 in mediating the leptin effects. Results: Compared with euthyroid rats, hypothyroid animals exhibited decreased overall glucose turnover and decreased glucose utilisation indices in skeletal muscle and adipose tissue. Leptinaemia in hypothyroid rats was lower while resistin mRNA expression in adipose tissue was higher than in euthyroid animals. Intracerebroventricular leptin infusion in hypothyroid rats partially restored overall, muscle and adipose tissue insulinstimulated glucose utilisation and improved the reduced glycaemic response observed during insulin tolerance tests. The leptin effects were due neither to the observed increase in plasma T3 levels nor to changes in the high adipose tissue resistin expression of hypothyroid rats. The administration of leptin to hypothyroid animals was accompanied by increased expression of muscle and adipose tissue carnitine palmitoyl transferases, decreased plasma NEFA levels and reduced muscle triglyceride content. Conclusions/interpretation: Hypothyroidism is characterised by decreased insulin responsiveness, partly mediated by an exaggerated glucose-fatty acid cycle that is partly alleviated by intracerebroventricular leptin administration.

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“…In these patients, one day treatment with a combination of iodide and PTU resulted in 50% greater decrease in plasma T3 than treatment with iodide plus methimazole. In euthyroid subjects, high doses of PTU cause a decrease in serum T3 ranging from 0 to 25% (22,77). Thyroidal D2 is also increased in Graves' thyroid tissues or in other forms of hyperthyroidism, despite elevated circulating levels of thyroid hormones, leading to an increase of intrathyroidal T4-to-T3 conversion (19).…”

Section: Deiodinases and Hyperthyroidismmentioning

confidence: 99%

Physiological role and regulation of iodothyronine deiodinases: A 2011 update

Marsili

Zavacki

Harney

et al. 2011

J Endocrinol Invest

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Thyroxine (T4) is a prohormone secreted by the thyroid. T4 has a long half life in circulation and it is tightly regulated to remain constant in a variety of circumstances. However, the availability of iodothyronine selenodeiodinases allow both the initiation or the cessation of thyroid hormone action and can result in surprisingly acute changes in the intracellular concentration of the active hormone T3, in a tissue-specific and chronologically-determined fashion, in spite of the constant circulating levels of the prohormone. This fine-tuning of thyroid hormone signaling is becoming widely appreciated in the context of situations where the rapid modifications in intracellular T3 concentrations are necessary for developmental changes or tissue repair. Given the increasing availability of genetic models of deiodinase deficiency, new insights into the role of these important enzymes are being recognized. In this review, we have incorporated new information regarding the special role played by these enzymes into our current knowledge of thyroid physiology, emphasizing the clinical significance of these new insights.

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Propylthiouracil blocks extrathyroidal conversion of thyroxine to triiodothyronine and augments thyrotropin secretion in man.

Cited by 188 publications

References 30 publications

Sequential deiodination of thyroxine in rat liver homogenate

Sequential deiodination of thyroxine in rat liver homogenate

Hypothyroidism in rats decreases peripheral glucose utilisation, a defect partially corrected by central leptin infusion

Physiological role and regulation of iodothyronine deiodinases: A 2011 update

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