Disease relevance of Thiouracil

• To elucidate the pathogenesis of thyroid gland hypervascularity in patients with Graves' disease, we studied the expression of mRNAs for vascular endothelial growth factor (VEGF) and its receptor, Flt family, using human thyroid follicles in vitro and thiouracil-fed rats in vivo [1].
• This dye is now shown to produce similar effects upon a modified form of aspartate transcarbamylase produced by Escherichia coli grown in a culture medium supplemented with thiouracil [2].
• Thiouracil distribution in mice carrying transplantable melanoma [3].
• The histological picture of the goiters was similar to that found in thiourea-treated teleosts and thiouracil-treated mammals [4].
• A microhemorrhagic process was consistently observed in association with the induction of thyroid hyperplasia by dietary thiouracil in the rat [5].

Psychiatry related information on Thiouracil

• Detection threshold for the taste of PROP (6-n-propyl thiouracil) in aqueous solution was determined in 173 French Caucasian women deprived of retronasal olfaction by blowing an air stream into the nostrils [6].
• The thiouracil-treated rats displayed reduced fearfulness in lever-touching and lever-pressing tasks in operant conditioning chambers and in their initial adaptation to activity-wheel and maze apparatuses [7].

High impact information on Thiouracil

• Feeding of the goitrogen, thiouracil, which stimulates secretion of thyroid-stimulating hormone, resulted in the appearance of some very narrow and some very wide, tight junctions or sometimes junctions with both wide and narrow regions within the same cell [8].
• The addition of ET-1 and ET-2 at 1-50 nM concentrations caused human melanocytes to significantly stimulate DNA [( 3H]thymidine incorporation) and melanin synthesis (3H2O release and [14C] thiouracil incorporation) [9].
• After goiter formation was induced by thiouracil and a low iodine diet, there was increased expression of the genes encoding ET-related proteins (ET-1, 3.2-fold; ETA, 2.9-fold; ETB, 3.5-fold) as well as two of the three NOS isoforms (NOS I, 2.7-fold; NOS III, 4.9-fold) [10].
• Over a period of 8 weeks, ram lambs were made hypothyroid (serum T4 less than or equal to 3 ng/ml compared with controls congruent to 30 ng/ml) by daily oral administration of methyl thiouracil or hyperthyroid (serum T4 congruent to 135 ng/ml) by daily sc injection of T4 [11].
• Capillary endothelial cell multiplication in adipose tissue pads on the thyroid during the feeding of thiouracil [12].

Chemical compound and disease context of Thiouracil

• Hypothyroidism was produced by administration of 4-methyl-2-thiouracil (thiouracil) in the drinking water for 2 weeks [13].
• Because ascorbic acid (AA) and the thyroid hormones are known to influence eggshell formation, the effects of AA on body weight, total plasma thyroxine (T4), egg production, and eggshell quality of Single Comb White Leghorn (SCWL) hens concurrently and previously treated with thiouracil (TU) were determined [14].
• Thioureylenes, such as thiouracil and methimazole, are known to be incorporated into growing melanin and selectively retained in melanotic melanoma [15].
• The effect of methionine, thiouracil, dienestrol diacetate and thyroprotein on the development and prevention of fatty liver in pullets [16].
• To be clinically useful in melanoma scanning, thiouracil has been radioiodinated, and 5-iodo-2-thiouracil (ITU) was found to be localized in melanotic melanoma as selectively as thiouracil [17].

Biological context of Thiouracil

• Lipolysis and blood capillary enlargement in adipose tissue pads on thyroids of rats fed thiouracil [18].
• Thiouracil and antibody titers of chickens from lines divergently selected for antibody response to sheep erythrocytes [19].
• Stimulation of the hexose monophosphate shunt activity in normal leucocytes during phagocytosis also was demonstrated with methimazole, thiouracil and thiourea, but not with adenine, uracil or urea [20].
• In both thiouracil-treated and thyroidectomized rats, body weights, kidney weight, arterial blood pressure, and pulse rate were decreased significantly v age-matched controls [21].
• Glomerular filtration rate was decreased, but filtration fraction and urinary excretion of albumin remained unchanged by thiouracil treatment and thyroidectomy [21].

Anatomical context of Thiouracil

• Thiouracil treatment delayed this progressive development of adjacent cell membrane interdigitation [22].
• Thiouracil treatment delayed the development of the corneal epithelium so that at stage 45 it resembled epithelium from a normal embryo 3 stages younger [22].
• It has been reported that blood capillaries in adipose tissue pads on the upper and lower poles of the thyroid gland enlarge when Fischer rats are fed thiouracil (TU) in a low iodine diet [12].
• Chick embryos were treated with thiouracil or thyroxine at stage 36 or 38; the corneas were excised 2 to 12 days after treatment (between stages 38 and 45), and prepared for electron microscopy [22].
• Effect of thiouracil upon canine arterial elastic tissue [23].

Associations of Thiouracil with other chemical compounds

• Thiourea, methylmercaptoimidazole, propylthiouracil, and thiouracil are all potent inhibitors of thyroid peroxidase (TPO)-catalyzed iodination [24].
• Theophylline stimulated melanin biosynthesis, as measured by rates of 2-[2-14C] thiouracil incorporation, and also caused an increase in the level of tyrosinase (EC 1.10.3.1) activity [25].
• Beagle dogs, 24 +/- 6 months old, fed a thiouracil-free semi-synthetic diet containing hydrogenated coconut oil and cholesterol (SS diet) for 12 months, developed marked hyperlipidemia and severe atherosclerosis [26].
• Hyperlipemia induced by high cholesterol and thiouracil was characterized by increased beta-lipoprotein (heparin-calcium and disc electrophoresis) [27].
• Interactions of horseradish peroxidase with propylthiouracil, thiouracil, propyluracil and uracil lead to the formation of complexes that exhibit different absorption spectra which can be attributed to the perturbation of peroxidase as the result of the drug-binding on a polar site in the protein [28].

Gene context of Thiouracil

• Normal TSH response to TRH was restored by partial thyroidectomy and in some cases by propyl thiouracil administration [29].
• The increase in PRL in the Thio, hCG-stimulated group coincides with formation of follicular cysts [30].
• Furthermore, genetic hypothyroidism does not appear to have nearly as marked an influence as thiouracil feeding on hypothalamic CRF levels [31].
• An attempt was also made to incorporate fluorescent thiouracil, since this would allow cells to be separated by FACS [32].
• S-Adenosylmethionine and the enzyme methionine adenosyltransferase were also increased by thiouracil [33].

Analytical, diagnostic and therapeutic context of Thiouracil

• Boron-containing thiouracil derivatives for neutron-capture therapy of melanoma [34].
• Thyroid activity was varied by hypophysectomy or by feeding a low iodine diet with or without added thiouracil [35].
• Thyroidectomy had the same effect as feeding thiouracil [36].
• These results illustrate the possible utility of radiolabeled thiouracil as a systemically administered brachytherapy agent for melanoma [37].
• Transplantable tumors of the thyroid gland have been produced by feeding of thiouracil (TU) to inbred Fischer 344 rats followed by the transplantation, initially, of pieces of hyperplastic thyroid gland, and in later generations, of pieces of transplanted tissue into similar rats or into rats fed a high iodine diet [38].

References