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.

β-Endorphin and its Congeners in Rat Pituitary and Thyroid: Effects of Propylthiouracil and Thyroid Hormone Administration*

Abstract: Immunoreactive β-endorphin (ir-βEP) and immunoreactive N-acetyl-endorphin (ir-NacEP) have been demonstrated in the rat thyroid by specific RIA and characterized by reverse phase HPLC In addition, pituitary and thyroid ir-βEP and ir-NacEP levels have been determined after manipulation of the pituitary-thyroid axis by chronic (21 days) treatment with 1) propylthiouracil (PTU), 2) l-T4, 3) l-T3, or 4) T3 plus PTU No difference in anterior pituitary or neurointermediate lobe ir-βEP was seen between controls and treated groups (n = 8/group) In contrast, levels of ir-NacEP were markedly lower (P < 001) in both hypo- and hyperthyroid groups than in controls, in both anterior pituitary and neurointermediate lobe In the thyroid, levels of both ir-βEP and ir-NacEP were profoundly depressed (P < 001) in all treated groups, with no change in calcitonin levels, suggesting that the thyroid effect of PTU and T3/T4 may be specific for the synthesis, processing, and/or release of pro-opiomelanocortin derived peptide

Polychlorinated biphenyls affect thyroid function and induce autoimmunity in Sprague-Dawley rats.

Abstract: Polychlorinated biphenyls (PCBs) have been reported to cause a variety of toxic effects. In order to assess the thyroid function after exposure to PCBs and investigate whether PCBs induce autoimmune process in the thyroid gland, we determined the levels of serum thyroid hormones (FT3, FT4, and T4), thyroid-stimulating hormone (TSH), and thyroid peroxidase antibody (TPOAb) in Sprague-Dawley rats treated with a commercial mixture of PCBs, Aroclor 1,254 (PCBs group), or the antithyroid drug, propylthiouracil (PTU group). The histopathology of the thyroid was also examined. Serum FT3, FT4, and T4 concentrations were significantly reduced, while TSH values were dramatically increased in PCBs group and PTU group compared with control rats (p 0.05). In contrast to the controls, treatment with PCBs lead to distinct histopathological changes in the thyroid gland, such as hyperplasia of the epithelia in follicles, colloid content reduction, vascularization, and lymphocytic infiltration in the perifollicular areas, whereas the major changes in the thyroid in PTU-treated rats were follicles shrinkage or collapse and colloid content reduction compatible with induced hypothyroidism. The results indicate that PCBs affect thyroid function via the induction of autoimmunity, which is a mechanism different from the effect of antithyroid drug on the thyroid gland.

Effects of thyrotropin-releasing hormone on serum concentrations of thyroxine and triiodothyronine in healthy, thyroidectomized, thyroxine-treated, and propylthiouracil-treated dogs.

Abstract: Effects of thyrotropin-releasing hormone (TRH) on serum concentrations of thyroid hormones were studied in 36 mixed-bred dogs. Dogs were randomly assigned to 7 groups. Significant increases (P less than 0.05) of serum thyroxine (T4) values occurred as early as 2 hours and reached a peak at 6 to 8 hours after IV injection of 300 to 1,100 micrograms of TRH. Thyroxine concentrations in response to a TRH dose greater than 500 micrograms were similar to those observed with the 300-micrograms dose. Transient coughing, vomiting, salivation, and defecation after large doses (900 and 1,100 micrograms) were observed. Mean serum T4 concentration decreased from 2.1 micrograms/dl to 0.9 micrograms/dl within 1 day of thyroidectomy. Clinical signs of hypothyroidism, including lethargy, dry coats, and diffuse alopecia, were present in 2 dogs at a month after surgical operation. Thyroxine concentrations were detectable for greater than 2 months. Injection (IV) of 700 micrograms of TRH 6 weeks after surgical operation had no effect on serum concentration of T4 in thyroidectomized dogs. In 5 T4-treated dogs, TRH (700 micrograms, IV) significantly increased the serum T4 value, indicating that pituitary thyrotropes were responsive to TRH, in spite of daily medication of 0.8 mg of T4. Four dogs were treated orally with 200 mg of propylthiouracil/day for 5 weeks. Intravenous injection of 700 micrograms of TRH in propylthiouracil-treated dogs had no effect on the serum T4 concentration, indicating that TRH had no effect on serum T4 values in these dogs during the experimental period. These results indicate that TRH can replace bovine thyrotropin for the canine thyroid function test.(ABSTRACT TRUNCATED AT 250 WORDS)

Site of Iodination in Hyperplastic Thyroid Glands Deduced from Autoradiographs

Abstract: We have tried to ascertain the site of iodination in the chronically stimulated, hyperplastic thyroid gland of rats. Rats were fed propylthiouracil in a commercial rat diet for 10 days. Then the diet was changed to a low iodine diet for 5 days. To label the gland, 10 mCi of 125I-iodide was injected into the left heart ventricle. Ten seconds later the animal was perfused through the left ventricle with a fixative solution containing a goitrogen to block further iodination, and stable iodide to help extract uncombined radioiodide. Electron microscopic autoradiographs prepared from the fixed thyroids show strong labeling over the lumen of the follicle and no consistent labeling of any other site or organelle. We conclude that the site of iodination in the chronically stimulated, hyperplastic thyroid is the follicular lumen, i.e. the same as that in the normal gland.

Thyroid over-expression of type 1 and type 2 deiodinase may account for the syndrome of low thyroxine and increasing triiodothyronine during propylthiouracil treatment.

Abstract: Although propylthiouracil inhibits type 1 deiodinase, leading to a more rapid fall in triiodothyronine (T3) than thyroxine (T4) levels in patients treated for hyperthyroidism, we report a patient with Graves’ disease whose free T3 paradoxically rose during such treatment, despite low free T4 levels and increasing doses of propylthiouracil. A similar response has previously been associated with high levels of thyroid stimulating antibodies, but it has been unclear why there should be a dichotomy in the circulating thyroid hormone profile. Thyroid tissue from our patient contained very high levels of type 1 and, especially, type 2 deiodinase, in contrast to other patients treated with Graves’ disease, which were most likely secondary to high levels of thyroid stimulating antibodies. This unusual response to propylthiouracil is important to recognise therapeutically, and represents a further situation in which abnormal expression of deiodinase enzymes has clinical significance.