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.
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TL;DR: Data suggest both different specificity and sensitivity among the myosin genes of different striated muscle types in response to thyroid hormone.
Abstract: In this study we examined the effects of 6-8 wk of thyroid hormone manipulation on striated muscle isomyosin expression in adult female rats. Animals were randomly assigned to one of three groups: 1) euthyroid controls, 2) thyroid deficient (propylthiouracil treated), and 3) hyperthyroid (triiodothyronine treated). Thyroid deficiency resulted in a marked increase in the low-adenosinetriphosphatase V3 isoform by 20- and 49-fold in the left and right ventricle, respectively. Conversely, hyperthyroidism induced a modest (3-11%) but significant increase in the high-adenosinetriphosphatase V1 isoform in both ventricles. The thyroid-deficient rats exhibited significant increases in slow myosin in both soleus (8%) and red gastrocnemius (24%), with concomitant reductions in intermediate myosin in both muscles. Interestingly, while the slow-myosin isoform was decreased in both the soleus (-19%) and the red gastrocnemius (-43%) of the hyperthyroid group, the intermediate-myosin isoform was affected differentially in the two muscles, with a fivefold increase in the former vs. a 16% decrease in the latter. Furthermore, hyperthyroidism increased the fast myosins in the red gastrocnemius while exerting no effect on the same isoforms in the white gastrocnemius. Collectively these data suggest both different specificity and sensitivity among the myosin genes of different striated muscle types in response to thyroid hormone.
50 citations
TL;DR: In animals treated with T4, with and without PTU, TSH suppression, alphaGPD activity and growth correlate better with serum T3 concentrations than with serumT4, suggesting that for maximum biologic activity, T4 must be converted to T3.
Abstract: To study the role of T4 to T3 conversion in the biologic action of T4, thyroidectomized, hypothyroid rats were given subcutaneous T4 (08 or 16 μg/100g/day) with or without intraperitoneal propylthiouracil (PTU) (1 mg/100g/day) Rats were killed after 5, 10, 12, or 15 days of treatment and serum T3 and T4 levels were correlated with serum TSH, liver mitochondrial αGPD activity and weight gain In rats killed at 5 days, PTU treatment resulted in higher serum T4, lower serum T3, and a markedly elevated serum T4:T3 ratio, demonstrating that PTU inhibits peripheral conversion of T4 to T3 in the rat Despite higher T4 levels, mean serum TSH was higher in the two groups receiving PTU as well as T4 In rats receiving 08 μg T4, growth rate was also slower with concomitant PTU administration In other groups of rats treated with 08 μg T4 for 10 and 15 days, PTU treatment resulted in similar differences in T3, T4, and T4:T3 ratios and serum TSH At 15 days, rats treated with 08 μg T4 + PTU had significantly lower αGPD activity than rats receiving 08 μg T4 alone PTU treatment had no effect on αGPD activity in rats maintained on 01 μg T3/100g/day indicating that there was no inhibition of this biologic response to T3 by this agent PTU without T4 had no significant effect on TSH, weight gain, or αGPD activity In addition, the dialyzable fraction of T3 and T4 in serum was not altered by this agent These data show that in animals treated with T4, with and without PTU, TSH suppression, αGPD activity and growth correlate better with serum T3 concentrations than with serum T4 This suggests that for maximum biologic activity, T4 must be converted to T3
50 citations
TL;DR: In a large population of euthyroid, hypothyroid, and hyperthyroid rats there was a linear correlation between serum TSH and the ratio in the hypothalamus of the concentration of 5- hydroxyindoleacetic acid (5-HIAA) to 5-HT.
Abstract: The aim of this study was to determine the specific roles of hypothalamic dopamine (DA), norepinephrine (NE), and serotonin (5-HT) in controlling the release of TSH in hypothyroid and euthyroid states in the rat. Selected ion monitoring (computerized gas chromatography/mass spectrometry) was used to assay, simultaneously, medial basal hypothalamic concentrations of DA, NE, and 5-HT and their major metabolites. The turnover of each amine in the hypothalamus of individual animals was estimated from the ratio of the concentration of metabolite to that of its precursor amine. In hypothyroid rats an increase in 5-HT turnover at various times after propylthiouracil (PTU) induction of hypothyroidism was associated with the expected rise in TSH secretion. In a large population (n = 90) of euthyroid, hypothyroid, and hyperthyroid rats there was a linear correlation between serum TSH and the ratio in the hypothalamus of the concentration of 5- hydroxyindoleacetic acid (5-HIAA) to 5-HT. The hypothesis that high hypo...
50 citations
TL;DR: The increasing incidence of toxic reactions following thiouracil therapy is well known today and as a substitute for this drug Astwood and Vanderlaan recommended propylthiouracic, and there were no significant side effects encountered.
Abstract: The increasing incidence of toxic reactions following thiouracil therapy is well known today. As a substitute for this drug Astwood and Vanderlaan 1 recommended propylthiouracil. There were no significant side effects encountered in their series of 100 cases. Reveno 2 in his observations on 54 patients found no evidence of toxic effect on the blood or blood-forming tissues. The only side effects encountered by the aforementioned authors were pruritus, urticaria and drug fever. Bartels 3 has given propylthiouracil to 450 patients at the Lahey Clinic with a toxicity incidence of 2 per cent. There has been 1 case of agranulocytosis, 5 cases exhibiting depressed leukocyte counts and 1 case revealing a typical fever response. In the reports received thus far, Hardy 4 knows of 1 case of agranulocytosis (Bartels') and states that a number of patients showed a drop in the leukocyte count, which soon rose despite the continuation of
50 citations
TL;DR: The data suggest that thyroid hormone permits endothelial cell proliferation in PAH, and a causal link between thyroid diseases and the onset or progression of vascular remodelling inPAH patients remains to be determined.
Abstract: Epidemiological evidence links pulmonary arterial hypertension (PAH) with thyroid disease, but a mechanistic explanation for this association is lacking. Because a central hallmark of vascular remodelling in pulmonary hypertension is lumen obliteration by endothelial cell growth and because thyroid hormones are known to be angiogenic, we hypothesised that thyroid hormones play a role in the control of endothelial cell proliferation in experimental PAH in rats. Hypothyroidism was induced by subtotal thyroidectomy and treatment with propylthiouracil (PTU) in rats with experimental PAH after combined exposure to vascular endothelial growth factor receptor inhibition and hypoxia (the Sugen-chronic hypoxia (SuHx) model). Subtotal thyroidectomy prevented and PTU treatment reversed the development of severe experimental PAH. Thyroxin repletion restored the PAH phenotype in thyroidectomised SuHx rats. The prevention of PAH by thyroidectomy was associated with a reduced rate of cell turnover, reduced extracellular signal-regulated protein kinases 1 and 2 phosphorylation, and reduced expression of α(v)β(3) integrin, fibroblast growth factor (FGF)-2 and FGF receptor. Thyroidectomy mitigated hypoxia-induced pulmonary hypertension, but this effect was not associated with a decreased pulmonary vascular resistance. These data suggest that thyroid hormone permits endothelial cell proliferation in PAH. A causal link between thyroid diseases and the onset or progression of vascular remodelling in PAH patients remains to be determined.
50 citations