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.

Ontogeny of the pituitary‐thyroid system in fetal rats: Observations on the fetal thyroid after maternal treatment with goitrogen

Abstract: The critical time of onset of the reciprocal relationship between the pituitary and the thyroid in fetal rats was assessed by the appearance of goiters in fetuses after maternal treatment with goitrogen, propylthiouracil (PTU), on various days of gestation. The assessment was based on changes in the weight and histology of the fetal thyroids. The day following overnight mating was regarded as day 1 of gestation. Pregnant rats were treated with 40 mg PTU each day for two days and autopsied on the third day. The various experimental periods were days 16--18, 17--19, 18--20, 19--21, and 20--22. PTU given to pregnant rats on days 16 and 17 did not cause any change in the fetal thyroids. PTU given on days 17 and 18 caused only a slight increase of fetal "thyroid weight/body weight" ratio. In all other experimental periods (days 18--20, 19--21, and 20--22), PTU induced conspicuous goiters in fetuses, which was reflected by an increased weight of thyroids, an increased height of follicular cells, and a decreased amount of colloid stored in follicles. The results suggest that in fetal rats, the reciprocal relationship between the pituitary and the thyroid is established on approximately days 19--20 of gestation.

Changes in TSH-immunoreactivity in the pars tuberalis and pars distalis of the fetal rat hypophysis following maternal administration of propylthiouracil and thyroxine.

Abstract: The pars tuberalis (pt) of the adenohypophysis is unique in its close spatial relationship to the neurohemal contact area of the median eminence. The morphology of pt-specific secretory cells does not resemble cell types of the pars distalis (pd); the functional role of these cells within the endocrine system is still unknown. One group of young mature female Wistar rats received propylthiouracil (PTU), a second group thyroxine (T4) (10 mg/l each in drinking water) from about 3 weeks prior to the expected pregnancy and throughout the experiment. On gestation day 20, the fetuses were obtained by laparatomy. Serial sections from the rostral portion of the pt and from the pd were immunostained using the peroxidase-antiperoxidase method. TSH concentrations were determined by RIA in serum and pituitaries; T4 was measured in serum. An antiserum against rat (r) TSH revealed a moderate positive reaction of nearly all cells of the pt in the control group. In both experimental groups the pt-specific cells showed weak or no immunoreactivity. Sections of all groups were negative with anti(r)-LH,-GH,-PRL. In contrast to controls, only a few immature TSH-cells could be found in sections of the pd in the T4-group, while concentrations of TSH in blood and hypophysis were very low. TSH-cells in the PTU-group were enlarged and less intensely stained. TSH-concentrations were decreased in the hypophysis, blood levels were elevated. All sections of the pd-specific cell populations showed positive immunoreactions with anti(r)-LH,-GH,-PRL. The present results suggest that pt-specific secretory cells of the fetal rat possess TSH immunoreactivity but do not resemble the thyrotropes of the pd. Marked differences in immunoreactivity displayed by the experimental groups indicate that pt-specific cells respond to changes in the fetal thyroid status and are a component of the thyroid-regulating system in addition to the thyrotropes of the pd. This novel aspect of pt function is discussed in connection with recent results concerning melatonin receptors found in the pt and the inhibitory influence of the pineal gland exerted on the thyroid gland.

Fatal agranulocytosis occurring during propylthiouracil therapy; report of a case.

Abstract: Shortly after the use of thiouracil as an antithyroid drug became common its potentialities as a depressant of polymorphonuclear cell formation became apparent. A number of cases were reported in which this complication resulted in death. The profession was cautioned that great care be exercised in its use and that frequent blood cell counts be done during the course of therapy. The development of propylthiouracil resulted from the search for a more potent and less toxic drug. Propylthiouracil is the only antithyroid drug listed in the 1948 edition of "New and Nonofficial Remedies." It is cautioned that this drug is capable of producing toxic reactions the severity of which is unpredictable—the most severe and serious one being agranulocytosis. That leukopenia can occur with the use of propylthiouracil has been mentioned in a number of articles. McCullogh, Hibbs and Schneider 1 reported 1 case of granulocytopenia in 218 cases studied. Eisenmenger

Anti-thyroid drugs and lymphocyte function: II. The in vivo effect on blastogenesis and suppressor cell activity in graves' disease

Abstract: The proliferative response (PR) of T lymphocytes in PHA stimulated cultures (5 μg/ml and 0·5 μg/ml; 72 hr) was used to assess the suppressive capabilities of peripheral blood mononuclear cells (PBMC) in the thyrotoxic phase of Graves' disease and their possible modification by propylthiouracil (PTU) and methimazole (MMI) treatment. Graves' patients had 50% higher PR than controls. Treatment with PTU (n=6) for 9·5 weeks (mean) or MMI (n=6) for 18 weeks (mean) resulted in continuous decrease in PR, starting after 3 weeks and down to control values and plateau at 7-10 weeks. This decrease correlated with the decline in plasma thyroxine (T4) levels which had already dropped by 3 weeks. Grouped according to thyroid functional state PR was significantly decreased only in the euthyroid state. Suppressor cell function, expressed as suppressor removal index (PR of PBMC pre-incubated for 24 hr/PR of fresh PBMC), was significantly lower in Graves' patients compared to controls and reached above normal values under PTU treatment: 0·98±0·16, 1·39±0·09 and 1·94±0·19 (mean±s.e.m.) respectively. A direct suppressive effect of PTU in culture, observed in normal subjects, did not exist in untreated patients and evolved under MMI treatment to above normal levels. The cell-mediated PTU effect, exercised by PBMC pre-incubated with PTU on autologous cells pre-incubated in medium alone, increased under PTU treatment to above normal levels. Both this cell-mediated suppressive effect and augmented PR of pre-incubated cells were already significantly increased after 3 weeks of PTU treatment, when all patients were still thyrotoxic. We conclude therefore that PBMC of patients in the untreated, thyrotoxic phase of Graves' disease are deficient in an active cell-mediated suppressive function, a deficiency corrected—with compensatory overshoot—during anti-thyroid drug treatment.

TSH-Induced Release of 5-Hydroxytryptamine and Histamine from Rat Thyroid Mast Cells

Abstract: The effect of TSH on rat thyroid mast cells was investigated by a combination of chemical, histochemical, electron microscopical, and bio-assay procedures. In T4-pretreated rats, a single iv injection of TSH reduced the concentration of 5-hydroxytryptamine (5-HT) and histamine in thyroid mast cells, whereas mast cells outside the thyroid seemed unaffected. In rats kept on propylthiouracil and iodine-poor diet for 4 weeks, plasma TSH levels were raised ten-fold. At the same time, follicle cells and mast cells in the thyroid increased in number, but the concentration of S-HT and histamine in individual thyroid mast cells was reduced. Ultrastructurally, there were no overt signs of mast cell degranulation, whether upon short-term or long-term TSH stimulation. It is concluded that, in the rat, TSH induces a release of 5-HT and histamine from intrathyroidal mast cells, which seems to occur without any concomitant degranulation. This release may be involved in the process of thyroid hormone secretion. (Endocrin...