scispace - formally typeset
Search or ask a question
Topic

Propylthiouracil

About: Propylthiouracil is a research topic. Over the lifetime, 2181 publications have been published within this topic receiving 46996 citations. The topic is also known as: Thyreostat® & 2,3-dihydro-6-propyl-2-thioxo-4(1H)-pyrimidinone.


Papers
More filters
Journal Article
TL;DR: Using the weight of the thymus as an indicator of general disturbances, it was found that not much difference seemed to exist in the toxicity of the four most effective goitrogenic compounds administered in equally effective doses.
Abstract: 1. Seventy-eight compounds were screened for goitrogenic action. Of these, 12 were found to be effective, but only thiouracil, propylthiouracil, 2-amino-thiazole and Dithane were found to be markedly active. 2. Of the four markedly goitrogenic compounds, propylthiouracil was the most effective, followed by thiouracil and Dithane. 2-Aminothiazole seemed to be less than half as active as thiouracil. 3. The weight of the thyroid gland, its iodine content and its microscopic appearance were all found to be equally useful criteria for goitrogenic action. 4. Many compounds caused general disturbances such as retardation or arrest in growth of the animals, atrophy or necrosis of the thymus and other lymphatic structures, and degeneration of various excretory and endocrine glands. It appears that these were phenomena of the general adaptation syndrome of Selye. 5. Evidence has been presented to show that the thymus is a most sensitive indicator of general disturbances of this kind, its weight being an excellent measure of the alarm reaction. 6. Using the weight of the thymus as an indicator of general disturbances, it was found that not much difference seemed to exist in the toxicity of the four most effective goitrogenic compounds administered in equally effective doses.

38 citations

Journal ArticleDOI
TL;DR: Since goitrogen treatment itself results in degranulation of the acidophils and thyrotrophs of the adenohypophysis, the effects of hypothalamic lesions per se on these cell types could not be determined in PTU-treated rats, and these unsolved problems prompted the currently reported investigation of the results of various hypothalamus lesions on rats which did not receive PTU.
Abstract: IN AN earlier report (Bogdanove and Halmi, 1953) we presented histo physiologic observations on the pituitary and target glands of rats which had been treated with propylthiouracil (PTU) following the placement of hypothalamic lesions. We were able to confirm Greer’s (1951, 1952) finding that certain hypothalamic lesions may prevent or impair PTUinduced thyroid hyperplasia. However, we never observed actual atrophy of this gland, and the question arose whether similar lesions would produce atrophy and/or decreased function of the thyroid in rats which did not receive any goitrogen. Further, since goitrogen treatment itself results in degranulation of the acidophils and thyrotrophs of the adenohypophysis, the effects of hypothalamic lesions per se on these cell types could not be determined in PTU-treated rats. These unsolved problems prompted the currently reported investigation of the effects of various hypothalamic lesions on rats which did not receive PTU.

38 citations

Journal ArticleDOI
TL;DR: It is more likely that inhibition of iodination by PTU in the rat thyroid involves competition between PTU and tyrosyl residues of thyroglobulin for oxidized iodine, comparable to the reversible mechanism of inhibition observed in the TPO model system.
Abstract: The antithyroid drug 6-propylthiouracil (PTU) was previously shown in our laboratory to have an unexpectedly prolonged inhibitory effect on iodination in the thyroid glands of rats. Eighteen hours after injection of a relatively small dose, iodination in the thyroid remained inhibited by more than 90%. We previously suggested that the prolonged inhibitory effect might be due to inactivation of thyroid peroxidase (TPO), a reaction previously shown to occur under certain conditions in an in vitro iodinating system containing highly purified TPO. However, the analytical procedure used in our earlier study did not exclude the possibility that sufficient PTU remained in the thyroid even after 18 h to inhibit TPO-catalyzed iodination by a reversible mechanism. Development of an improved analytical procedure, based on HPLC, led us to reexamine the mechanism of the prolonged inhibitory effect of PTU on iodination in rat thyroid glands. Rats were injected with [35S]PTU (1 mumol/100 g BW), and ultrafiltrates prepared from their homogenized thyroid glands were analyzed by HPLC. The major 35S-labeled metabolites were identified as sulfate/sulfite, PTU sulfinate, and PTU sulfonate. However, even after 18 h, a significant amount of unchanged [35S]PTU was also present. The calculated mean concentration of residual PTU was 20 microM, a sufficiently high level to explain the observed inhibition of iodination on the basis of a reversible mechanism. Experiments were also performed to examine the intrathyroidal distribution of 35S at intervals after the injection of [35S]PTU. All of the oxidation products of PTU showed marked increases between 2 and 16 h after injection. Based on our view that TPO is the major mediator of intrathyroidal metabolism of PTU, this observation is inconsistent with our previous proposal that TPO is inactivated after PTU injection. The results of the present study, therefore, lead us to withdraw our previous suggestion that TPO is inactivated after injection of PTU into rats. It is more likely that inhibition of iodination by PTU in the rat thyroid involves competition between PTU and tyrosyl residues of thyroglobulin for oxidized iodine, comparable to the reversible mechanism of inhibition observed in the TPO model system.

38 citations

Journal ArticleDOI
TL;DR: It appears T3SO4 has no intrinsic biological activity, but, under certain circumstances, may be reactivated by desulfation.
Abstract: Hepatic microsomes and isolated hepatocytes in short term culture desulfate T3 sulfate (T3SO4). We, therefore, wished to determine whether T3SO4 could mimic the action of thyroid hormone in vitro. T3SO4 had no thyromimetic effect on the activity of Ca(2+)-ATPase in human erythrocyte membranes at doses up to 10,000 times the maximally effective dose of T3 (10(-10) mol/L). In GH4C1 pituitary cells, T3SO4 failed to displace [125I]T3 from nuclear receptors in intact cells or soluble preparations. Thus, T3SO4 was not directly thyromimetic in either an isolated human membrane system or a pituitary cell system in which nuclear receptor occupancy correlates with GH synthesis. Thyroid hormones inhibit [3H]glycosaminoglycan synthesis by cultured human dermal fibroblasts, and T3SO4 displayed about 0.5% the activity of T3 at 72 h. Human fibroblasts contained roughly the same level of microsomal p-nitrophenyl sulfatase activity as that previously observed in hepatic microsomes. Propylthiouracil (50 mumol/L) did not af...

37 citations

Journal ArticleDOI
TL;DR: Analysis of ten fully documented cases of aplastic anemia associated with use of the antithyroid drugs methimazole, carbimazoles, and propylthiouracil indicated that the disorder is typically characterized by severe pancytopenia and profound marrow hypoplasia, yet surprisingly good prognosis, ie, minimum survival of more than 70% with partial or complete recovery from symptoms and cytopenias in survivors within 2-5 weeks.

37 citations


Network Information
Related Topics (5)
Hormone
38.3K papers, 1.2M citations
81% related
Thyroid
68.8K papers, 1.5M citations
80% related
Leptin
22.7K papers, 1.1M citations
78% related
Estrogen
40.7K papers, 1.7M citations
77% related
Secretion
24.8K papers, 1.2M citations
75% related
Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202342
202276
202138
202032
201934
201829