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.

The effect of the thyroidal state on the immunological state of the chicken.

Abstract: Effects of the thyroidal state on certain immunological parameters were studied in four groups of male White Leghorn chicks. One group was fed with commercial chick mash and served as control, the second was supplemented with 0.1 % Propylthiouracil (PTU) in food, the third was supplemented with 0.025 % thyroxine in food, and the fourth was supplemented with 0.1 % PTU and 0.025 % thyroxine. Treatment with PTU (29 days) resulted in hypothyroidism evidenced by low T4 level, decreased oxygen consumption rate and decreased weight gain. Thyroxine treated group reached hyperthyroidism shown by high T4 level and increased oxygen consumption rate. When all chicks were immunized with SRBC, hemagglutinating antibody titer of PTU treated group was significantly lower than that of the other group while thyroxine treatment resulted in increased, but statistically not significant titers. At 36 days of age the chicks were killed. PTU treated group exhibited decreased thymus, spleen and bursa weights and low 3H thymidine incorporation after Con A stimulation of both spleen and thymus cells. Thyroxine treatment resulted as well in low 3H thymidine incorporation. These findings indicated that hypothyroidism depressed the immunological system, while hyperthyroidism had no effect on antibody formation but depressed reactivity to Con A stimulation.

Thyroid Hormone and Cell Formation in the Developing Rat Cerebellum

Abstract: Effects of neonatal hyperthyroidism on cell formation in the developing rat cerebellum were reinvestigated. Administration at birth of excessive doses of thyroxine or triiodothyronine led to an early stimulation of cell acquisition, followed by a permanent deficit of cells in the cerebellum. The corrective effects of physiological doses of thyroxine on the troubles of the histological and biochemical development of the cerebellum in thyroid-deficient animals were also studied. As early as 6 days, cell maturation and formation were already retarded in animals treated with propylthiouracil, but, as previously reported, cell formation was prolonged and the final number of cells was normal. Administration to thyroid-deficient animals of progressively increasing doses of thyroxine, nearly equal to the amounts of hormone secreted by the thyroid gland of the developing normal rat, returned the evolution of the cerebellar wet weight and of the cerebellar DNA to normal, as well as the histological maturation of the cerebellum, even if it did not entirely correct the retardation of body growth. These results are consistent with the view that thyroid hormone early stimulates maturation of the cerebellar germinative cells and subsequently interacts with cell formation in the cerebellum, and that this action is physiological.

Thyroid hormone modulation of thyrotrophin-releasing hormone (TRH) and TRH-gly levels in the male rat reproductive system

Abstract: Thyrotrophin-releasing hormone (TRH) occurs in high concentrations in the rat ventral prostate and its concentrations is regulated in a positive dose-response manner by testosterone in castrated rats. alpha-Amidation of the tetrapeptide precursor, TRH-Gly, is a rate-limiting step in TRH biosynthesis. To investigate further the hormonal regulation of TRH biosynthesis in prostatic tissue, Sprague-Dawley rats of approximately 250 g were injected s.c. with either physiological saline or 3 mg propylthiouracil (PTU) daily for 5 days. The reproductive tissues were boiled in acetic acid (l mol/l), dried and extracted with methanol. The methanol extracts were measured for TRH immunoreactivity (TRH-IR) and TRH-Gly-IR by radioimmunoassay. Hypothyroidism induced by PTU significantly increased TRH-IR and TRH-Gly-IR levels in prostate and testis and reduced these levels in epididymis but did not affect the serum concentrations of testosterone compared with those of controls. Corresponding changes in TRH and TRH-Gly in the rat prostate were established by high-pressure liquid chromatography. To control for possible pharmacological effects of PTU on TRH biosynthesis, additional experiments were carried out on castrated rats receiving testosterone replacement and treatment with PTU plus methimazole. Treatment with thyroxine (T4) significantly reduced the increase in prostatic TRH levels due to hypothyroidism, despite the drug-induced blockade of the conversion of T4 to tri-iodothyronine. These effects parallel similar observations made in rat spinal cord and pancreas. This study demonstrates that in the male rat reproductive system the levels of TRH and its immediate biosynthetic precursor, TRH-Gly, are regulated by thyroid hormones.

Induced hypothyroidism accelerates the regression of liver fibrosis in rats

Abstract: Background and Aim: It has been shown in previous studies that hypothyroidism pre- vents the development of liver fibrosis in bile duct ligated rats and in rats chronically treated with thioacetamide (TAA). In recent years, regression of liver fibrosis (occurring sponta- neously or during treatment) has been demonstrated in rodent models such as bile duct ligation and CCl4 administration. Therefore, in the present study, the potential therapeutic effect of hypothyroidism on liver fibrosis was investigated. Methods: Liver fibrosis was induced in rats by administration of TAA (200 mg/kg, i.p., twice weekly) for 12 weeks. Hypothyroidism was then induced by either methimazole (0.04%) or propylthiouracil (0.05%) administered in drinking water for 8 weeks. Control euthyroid rats received normal drinking water. Hypothyroidism was confirmed by a sig- nificant elevation of serum thyroid-stimulating hormone levels. Results: Eight weeks after the cessation of TAA administration, spleen weight, histologi- cal score of liver fibrosis, and hepatic hydroxyproline content were significantly lower in both groups of hypothyroid rats as compared to euthyroid controls (P < 0.001). In vitro studies using the rat hepatic stellate cell line HSC-T6 using northern blot analysis and zymography, respectively, showed that high concentrations of triiodotyronine (T3) enhanced transforming growth factor (TGF)-b-induced collagen I gene expression, and reduced metalloproteinase (MMP)-2 secretion, implying that reducing the levels of T3 may contribute to resolution of fibrosis. Additionally, low T3 concentration inhibited HSC-T6 proliferation. Conclusion: Pharmacologically induced hypothyroidism accelerates the resolution of liver fibrosis in rats. This beneficial effect may in part be due to prevention of T3-induced stimulation of collagen synthesis and reduction of MMP-2 secretion.

The effects of thyroid status on plasma leptin levels in women

Abstract: Leptin, the product of the adipose specific ob gene, regulates food intake and energy expenditure. However, little is known about the effects of thyroid status on plasma leptin levels in women. We determined fasting plasma leptin levels before and 1 month after restoration of euthyroidism in 20 female patients with hypothyroidism, 20 female patients with hyperthyroidism and 20 age and BMI — matched female controls. To restore the normal thyroid function patients with hypothyroidism were treated with levothyroxine, whereas patients with hyperthyroidism were treated with propylthiouracil. Plasma leptin levels were measured by a RIA method with a sensitivity of 0.5 µg/l. Leptin levels were significantly lower in patients with hypothyroidism before treatment (4.17±2.58 µg/l) than in patients with hyperthyroidism (6.80±4.3 µg/l; z= −2.06, p=0.037). Leptin levels were significantly higher in hyperthyroid patients than in the control group (3.71±1.69 µ/l, z= −2.44, p=0.014) whereas leptin levels in the hypothyroid patients were not significantly different from those in control subjects (z= −0.16, p=0.87). Restoration of euthyroid state was not associated with a significant change in leptin levels either in the hypothyroid (from 4.17±2.58 to 5.22±3.4 µg/l; z= −1,74, p=0.08) or in the hyperthyroid group (from 6.80±4.37 µg/l to 7.93±6.25 µg/l z= −0.89, p=0.37), although a tendency for leptin to increase was observed in both groups. There was no correlation between plasma leptin and FT3, FT4, TSH, or BMI either before or after therapy in both groups. Leptin levels were significantly correlated with BMI in the control group (r= −0.53, p=0.018). We conclude that plasma leptin levels are increased in hyperthyroidism and unchanged in hypothyroidism. Furthermore, our study demonstrates that mean plasma leptin levels are not influenced by short term restoration of euthyroidism in both hypothyroidism and hyperthyroidism, although an effect of long-term treatment may not be excluded.