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PubMed1984

Propylthiouracil, ipodate, dexamethasone and periods of fasting induce different variations in serum rT3 in dogs.

Fasting or administration of propylthiouracil (PTU), ipodate, or dexamethasone are all known to induce a pattern of low serum triiodothyronine (T3) concentrations and high serum reverse T3 (rT3) concentrations in humans. In the present study it was found that this is not a universal phenomenon. In normal dogs exposed to fasting or these various pharmacologic agents, the serum T3 level was always depressed as in humans. However, different variations in serum rT3 levels were observed. Fasting and PTU administration were accompanied by slight decreases in the serum rT3 concentration. A single dose of ipodate did not alter serum rT3 levels, but serum thyroxine (T4) levels increased by more than 50%. Dexamethasone induced a considerable increase in serum rT3 levels, while serum T4 levels were unaltered. The results suggest that the high serum rT3 level nearly always seen in "the low T3 syndrome" in humans is merely a coincidental character of the human species, and that it has little importance for in vivo homeostasis.

Animals↗

PubMed1992

Facial expressions and genetic sensitivity to 6-n-propylthiouracil predict hedonic response to sweet.

Individuals differ in their hedonic response to sweet: sweet likers show increasing liking with increasing sucrose concentration, while sweet dislikers show increasing dislike with increasing concentration. Our results indicated that naive raters can correctly classify sweet likers and dislikers by observing subjects' facial responses to the taste of sucrose. Also, for both adults and children, the sweet liker/disliker distinction correlated strongly with the genetically determined ability to taste 6-n-propylthiouracil (PROP): PROP nontasters were almost always sweet likers, whereas sweet dislikers were almost always PROP tasters. Sweet dislikers also reported a purer sweet sensation than likers, who perceived nonsweet components in pure sucrose solutions. These results suggest that the sweet liker/disliker distinction is robust and valid, and that sensitivity to PROP may influence preference for sweet by altering the quality of sweet.

Adolescent↗

PubMed1975

Effect of partial thyroidectomy, propylthiouracil or thyroxine on estrogen-induced intranuclear inclusions in mammotrophs of the Mongolian gerbil.

Partial thyroidectomy caused a significant increase in the number of intranuclear inclusions per field (2-83 +/- 0-10 inclusions as compared with 0-15 +/- 0-03 inclusions for sham-controls). The inclusions occurred exclusively within mammotrophs. Thyrotrophs were stimulated: an increased cell size, numerous secretory granules, an enlarged Golgi apparatus and hypertrophic rough endoplasmic reticulum. Propylthiouracil caused similar ultrastructural changes although sighificantly fewer inclusions were observed (0-64 +/- 0-06 inclusions). Suppression of thyroid function with thyroxine produced no change in the number of inclusions (0-17 +/- 0-03 inclusions) although when combined with estrogen there were significantly fewer inclusions (1-62 +/- 0-07) when compared to estrogen alone (2-69 +/- 0-09). Intranuclear inclusions appear to be a unique reaction of mammotrophs to cellular hyperfunction in the Mongolian gerbil.

Animals↗

PubMed1986

Antithyroid effects of propylthiouracil and sulfamonomethoxine in rats and monkeys.

Experiments were performed to investigate the species difference in antithyroid effects of propylthiouracil (PTU) and sulfamonomethoxine (SMM). Sprague-Dawley rats were administered 30 mg/kg of PTU, or 30 or 270 mg/kg of SMM orally for 5 weeks, while squirrel monkeys received 30 mg/kg of PTU or 270 mg/kg of SMM. In rats receiving 30 mg/kg of PTU, a decrease of both serum 3,5,3'-triiodothyronine and thyroxine concentrations and of 131I incorporation into the thyroid hormone precursors was observed, together with elevation of serum thyroid-stimulating hormone concentration, an increase in thyroid weight, and hyperplasia of the follicular epithelium of the thyroid gland. Similar changes were seen in rats receiving 270 mg/kg of SMM; however, the antithyroid effects of SMM were less severe than those of PTU. No change was produced in monkey thyroids by 5-week treatments with 30 mg/kg of PTU or with 270 mg/kg of SMM. The molar concentration of PTU required for the in vitro inhibition of thyroid peroxidase was markedly lower in rats than in monkeys. SMM showed a similar species difference in the inhibition of thyroid peroxidase in vitro, but the enzyme inhibition of SMM was weaker than that of PTU. These findings suggest that rats were more sensitive to the antithyroid effects of PTU and SMM than monkeys, and that inhibition of thyroid peroxidase may play an important role in species difference in the antithyroid effects of the two drugs.

Animals↗

PubMed1991

Comparison of the effects of propylthiouracil, amiodarone, diphenylhydantoin, phenobarbital, and 3-methylcholanthrene on hepatic and renal T4 metabolism and thyroid gland function in rats.

We studied the effects of propylthiouracil (PTU), amiodarone (AMIO), diphenylhydantoin (DPH), phenobarbital (PB), and 3-methylcholanthrene (MC) on thyroid histomorphology, on the hepatic and renal enzymes involved in endogenous and exogenous metabolism, and on the plasma levels and pharmacokinetics of thyroid hormones after 7 and 14 days of treatment. PTU and PB, by decreasing both serum tetraiodothyronine (T4) and triiodothyronine (T3), induced a massive increase in serum thyrotropin (TSH) and thus induced thyroid hypertrophy. AMIO and MC, by decreasing respectively serum T3 and T4, also induced an increase of TSH, but to a lesser extent, not sufficient to induce thyroid hypertrophy. Hepatic 5'-deiodinase activity was decreased in all treated rats. Inhibition of this enzyme by PTU was demonstrated in vitro; AMIO also decreased the enzyme activity by a still unelucidated mechanism, which probably requires intact cell plasma membranes, whereas in PB- and MC-treated rats the decrease in enzyme activity certainly resulted from decreased serum concentrations of T4. In PTU-treated rats, and probably in MC-treated rats, decreases in circulating thyroid hormones were primarily due to impairment of synthesis and/or of secretion by the thyroid. In contrast, in PB-treated rats, the decrease in serum thyroid hormone levels seems to be due to increased excretion of these hormones, as T4 serum clearance was significantly increased. PB, a microsomal enzyme inducer, increased the cytochrome b5 and P450 content as well as the cytochrome P450-dependent O-depentylation of pentoxyresorufin. The other type of enzyme inducer, MC, did not affect cytochrome b5 and P450 levels, but did increase the cytochrome P450 dependent O-deethylation of ethoxyresorufin. PB increased the glucuronidation of morphine, whereas MC increased the glucuronidation of 1-naphthol. However, serum T4 clearance, mainly determined by its hepatic conjugation rate, was increased only in PB-treated rats. It appears from this study that the close metabolic relationship between the liver/kidney and the thyroid should be taken into consideration when the findings of chronic toxicology and carcinogenicity studies are interpreted.

Amiodarone↗

PubMedDate not supplied

Thyroxine and propylthiouracil-induced changes in the activity of monoamine oxidase in the fetal rat.

The activity of monoamine oxidase (MAO) towards tryptamine has been determined in heart, brain and liver of the 21.5 day old rat fetus. The activity was compared between normal, thyroxine and propylthiouracil (PTU) treated animals. Hypothyroidism induced by PTU leads to a decrease in the activity of the three organs, while hyperthyroidism causes an increase in the enzymatic activity. These differences seem to be rather independent of the protein content of the organs. It appears thar rat fetal MAO is under a strong thyroid control.

Animals↗

PubMed1988

Effects of propylthiouracil (PTU) on the immunological status of the chicken.

Effects of propylthiouracil (PTU) using different treatment schedules on immune functions in young male chicken were studied. Antibody productions to sheep red blood cells (SRBC) and Brucella abortus (BA) were found to rise in the chicks treated with 0.1% and 1% PTU. Furthermore, the chicks treated with 1% PTU exhibited a significantly greater reaction to phytohemagglutinin (PHA) in skin test using the wing web than the control did. Treatment of 5% PTU, however, inhibited the antibody productions to SRBC and BA and the reaction for the skin test to PHA. Antibody titers to both antigens and serum IgG level were lower in the chicks after cessation of PTU treatment. The most conspicuous histology was the lymphatic depletion of the lymphoid organs in chicks treated with 5% PTU. The bursa of Fabricius, thymus and spleen were severely atrophied. The total WBC and the number of lymphocytes and monocytes were significantly reduced in the presence of 0.1% and 1% PTU at 8 weeks of age. Although, concentrations of serum thyroxin (T4) and 3,5,3'-triiodothyronine (T3) were significantly lower in the chicks treated with all doses of PTU, the cessation of the treatment was followed by an increase in the concentrations of serum T4 and T3 to levels not different from in the untreated control chicks. These data showed that PTU at 0.1% and 1% concentrations did not suppress immune responses in chickens unlike the case reported in mammals.

Animals↗

PubMed1993

Effects of hypothyroidism with treatment of an anti-thyroid drug, propylthiouracil on immune responses in chickens.

The effect of a wide range of doses of propylthiouracil (PTU, 0.01-5%) on the immune responses of young male chickens was examined. One-day-old chickens were rendered hypothyroid by PTU supplemented in the feed for 4 weeks. At all doses PTU treatment caused a significant dose-related reduction in body weight (except at 0.01%) and in relative lymphoid organ weights. Skin response to phytohemagglutinin (PHA) was significantly greater in the chickens treated with low doses of PTU (0.01-0.1%) and significantly less in the chickens treated with high doses of PTU (1.5-5%) than that in control chickens. Number of splenic plaque forming cells (PFC) to sheep red blood cells (SRBC) was significantly increased in the chickens treated with low doses of PTU. Concentrations of serum 3,3',5-triiodothyronine (T3) and thyroxin (T4) were significantly lower in the chickens treated with all doses of PTU. Addition of T3 to the feed supplemented with 0.01% PTU replaced the serum T3 concentration and reduced the skin response to PHA and the number of the splenic PFC. These data confirm our previous observations that a low dose of PTU enhances and a high dose suppresses the immune responses of young male chickens.

Adrenal Glands↗

PubMed1990

Postnatal development of the wild-type and weaver cerebellum after embryonic administration of propylthiouracil (PTU).

In this study we used propylthiouracil (PTU), a thyroid hormone-inhibiting compound, to render +/+, wv/+, and wv/wv embryos hypothyroid in order to test if the appearance of external granule layer (EGL) cell death in the weaver cerebellum is affected by alteration of granule cell development. At birth, the number of EGL cells in the PTU-treated cerebellum was reduced, compared to control animals, by 50%. Also, the amount of cell death was reduced in the PTU-treated wv/wv cerebellum. As adults, no differences were seen between PTU-treated and untreated mutant or normal cerebella. If the hypothyroid treatment that results in a 50% decrease in EGL cell number is due to an extension of cell cycling time, then the expression of the weaver phenotype of cell death likely follows granule cell exit from the cell cycle.

Animals↗

PubMed1993

Propylthiouracil in psoriasis: results of an open trial.

BACKGROUND: Propylthiouracil (PTU) is an antithyroid thioureylene that has immune modulatory and free radical scavenging abilities. In view of the immunomodulatory effects of PTU, we decided to study the therapeutic response of patients with psoriasis to oral PTU. OBJECTIVE: Our purpose was to study the effect of oral PTU in patients with stable plaque psoriasis. METHODS: Oral PTU, 100 mg, was administered every 8 hours for 8 weeks to 10 patients with long-standing psoriasis. Skin biopsy specimens were taken from the lesions before and at the end of the study. Clinical response was monitored with the Psoriasis Area and Severity Index scoring system. Histologic scores were graded with a 5-point grading scale. Complete blood cell count was obtained at the beginning and at the end of the study. Thyroid-stimulating hormone (TSH) was obtained at the beginning and every 2 weeks thereafter until completion of the study. RESULTS: Three patients dropped out of the study. Of the remaining seven, two showed near-complete resolution of their psoriatic lesions, whereas the remainder showed moderate improvement in their clinical scores. Histologic scores were significantly improved in the group with all but one patient showing improvement or no change. Thyroid function tests were unchanged in all but one patient who showed a slight increase in serum TSH at the sixth week of therapy. CONCLUSION: Because of its low toxicity relative to other oral treatments of psoriasis, PTU may have a role in the treatment of patients with this disorder.

Administration, Oral↗

PubMed1985

Changes in the hemoglobin system of the coho salmon Oncorhynchus kisutch during smoltification and triiodothyronine and propylthiouracil treatment.

Three electrophoretically separable forms of blood hemoglobin were found in fry of coho salmon (Oncorhynchus kisutch). Ten hemoglobin forms were found in juvenile and adult salmon. Treatment of yearling salmon with triiodothyronine (T3) at 12 ppm in the diet accelerated the increase in concentration of adult forms of hemoglobin, while treatment with T3 at 4 ppm had no effect. Dietary propylthiouracil (1.5 or 5 mg/g) reduced the increases in adult forms of hemoglobin during smoltification. These results implicate thyroid hormones in the expression of adult forms of hemoglobin during the parr to smolt transformation of juvenile salmon.

Aging↗

PubMed1991

Methimazole and propylthiouracil increase thyroglobulin gene expression in FRTL-5 cells.

In FRTL-5 cells, methimazole (MMI) and propylthiouracil (PTU), both thyroid peroxidase (TPO) inhibitors, increase thyroglobulin (Tg) mRNA levels and Tg accumulation in the medium. An increase in Tg mRNA levels and in Tg accumulation was observed after 2-4 h and 8 h incubation with 10,000 microM MMI or PTU, respectively. Glutamate dehydrogenase mRNA levels, which corresponded with total RNA levels, were not affected. The concentrations of these drugs at which stimulation occurs are higher than the concentrations required for complete inhibition of TPO activity. The stimulatory effects of MMI and PTU can be suppressed by iodide and do not occur when protein synthesis is inhibited by cycloheximide. The effect of MMI on Tg gene expression is not dependent on thyrotropin (TSH) or insulin and MMI does not change the TSH-induced cAMP production. We conclude that MMI and PTU interfere in a regulatory pathway for Tg gene expression.

Cell Line↗

PubMed1996

Propylthiouracil treatment reduces long-term potentiation in area CA1 of neonatal rat hippocampus.

Rat pups were made hypothyroid by exposure to propylthiouracil in drinking water beginning at 1 week of age, and the degree of long-term potentiation (LTP) in hippocampal area CA1 determined from brain slices of animals ranging in age from 2 to 6 weeks. Serum T3 levels were less than 20% of that of age matched controls after 3 weeks of treatment, and remained at that level. Relative to the age-matched controls, LTP was reduced significantly after 2 weeks of treatment. These observations are consistent with the conclusion that LTP magnitude is a reflection of cognitive function, which is known to be depressed in hypothyroid conditions in both animals and man.

Administration, Oral↗

PubMed1978

Change of the protein composition of the thyroid colloid during treatment with propylthiouracil and thyroxine: a microgel electrophoretic study of single rat thyroid follicles.

Prophylthiouracil and thyroxine were given daily to rats for 4 weeks. Samples of colloid were collected in vivo from the superficial thyroid follicles during this period and their protein composition was analysed by gel electrophoresis. It was observed that the aggregates of thyroglobulin, i.e., the 27-S thyroid iodoprotein and the heavier fractions, were reduced to 50% after 1 week and were almost absent after 2 weeks. A faster migrating thyroglobulin fraction was observed in the samples of colloid and in the homogenate of the whole gland after 48 h of treatment. During the following period of treatment there was an increase in the relative amount of the faster migrating thyroglobulin fraction compared to 19-S thyroglobulin in the colloid, the former comprising approx. 75% of the globulins after 4 weeks, It can be concluded that propylthiouracil inhibits the formation of the 27-S iodoprotein and that a structurally altered and iodine-poor thyroglobulin fraction is accumulated in the follicle lumen.

Animals↗

PubMed1976

A comparison of the effect of propylthiouracil on the respiration of thyroid slices from humans, chickens and rats.

1. The QO2 of thyroid slices from hyperthyroid patients treated with propylthiouracil (PTU) was 140% that of slices from euthyroid patients. Similar results were obtained using thyroid slices from PTU fed and control chickens. 2. PTU feeding caused thyroid hyperplasia, increased QO2 more than could be accounted for by the hyperplasia but neither increased QO2 of muscle, cerebral cortex or spleen nor altered serum T4 levels. 3. PTU in drinking water increased the size and vascularity of thyroids from control but not hypophysectomized rats and had no effect on QO2. 4. The observations made on human, chicken and rat thryoid apparently reflect the effects of TSH rather than a direct action of PTU.

Adolescent↗

PubMed1989

Effects of ethanol and propylthiouracil on hepatic iron and copper contents in the male albino mouse.

With the aim to analyze whether propylthiouracil (PTU) alters ethanol-induced changes in liver iron and copper contents, 40 male albino mice were equally divided into a control group, an ethanol-treated group, a PTU-treated group and an ethanol + PTU-treated group. Twenty animals were killed at the age of 85 days and 20 at the age of 180 days. Liver iron and copper contents showed a progressive, statistically non-significant increase both in the controls and in ethanol-treated animals. Liver iron contents was significantly higher in the 180-day-old alcoholic mice as compared with controls. Animals treated either with PTU or with PTU + ethanol showed liver iron levels in the normal range, markedly different from the ethanol-treated animals (P less than 0.005). Liver copper content of the ethanol-treated animals was higher (but not significantly) than that of the controls. Liver copper levels of the PTU + ethanol-treated animals were in the range of the ethanol-treated animals. Thus, PTU seems to revert an overload of ethanol-mediated iron of copper.

Alcoholism↗

PubMed1992

Relationships between the thyroid and somatotropic axes in steers. I: Effects of propylthiouracil-induced hypothyroidism on growth hormone, thyroid stimulating hormone and insulin-like growth factor I.

The effects of propylthiouracil (PTU)-induced thyroid hormone imbalance on GH, TSH and IGF-I status in cattle were examined. In the first study, four crossbred steers (avg wt 350 kg) were fed a diet dressed with PTU (0, 1, 2 or 4 mg/kg/d BW) in a Latin square design with four 35-d periods. On day 29 in each period, steers were challenged with an intrajugular bolus of thyrotropin releasing hormone (TRH, 1.0 microgram/kg). Blood samples were obtained to assess the change in plasma GH and TSH as affected by PTU. Plasma IGF-I was measured from blood samples obtained before and after (every 6 hr for 24 hr) intramuscular injection of bovine GH (0.1 mg/kg, day 31). Doses of 1 and 2 mg/kg PTU increased plasma T4 (P < .01). At 4 mg/kg, PTU depressed T4 concentrations to 30% of control (P < .01). Plasma T3 linearly decreased with increasing doses of PTU (P < .01). Plasma TSH increased when PTU was fed at 4 mg/kg (P < .05) while the TSH response to TRH declined with increasing PTU (P < .02). Neither basal nor TRH-stimulated plasma concentration of GH was affected by PTU; the IGF-I response to GH tended to increase at the 1 and 2 mg/kg PTU (P < .01). In a second study 24 crossbred steers were fed PTU (1.5 mg/kg) for 119 d in a 2 x 2 factorial design with implantation of the steroid growth effector, Synovex-S (200 mg progesterone + 20 mg estradiol), as the other main effect. Basal plasma GH and IGF-I were not affected by PTU treatment. Synovex increased plasma concentration (P < .01) of IGF-I without an effect on plasma GH. The data suggest that mild changes in thyroid status associated with PTU affects regulation of T3, T4 and TSH more than GH or IGF-I in steers.

Animals↗

PubMed1994

Serum hormones during the estrous cycle and estrous behavior in heifers after administration of propylthiouracil and thyroxine.

Two experiments were conducted to assess the characteristics of thyroid-stimulating hormone (TSH) during the estrous cycle and to examine the effects of experimentally altered thyroid status on estrous behavior and hormonal concentrations in heifers. In Exp. 1, normal profiles of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and TSH were examined on days 2, 12, and 19 of the estrous cycle (day 0 = estrus) in six Holstein heifers. Baseline concentrations of LH were 1.5- to 2.1-fold higher on day 2 (P = .07) and day 19 (P < .01) than on day 12. Pulse frequency of LH was higher (P < .05) on days 12 and 19 than on day 2. For FSH, baseline concentrations were similar on all 3 d, but pulse frequency was higher (P < .05) on day 19 than on day 2 or day 12. Overall and baseline concentrations of TSH were similar on all 3 d. Pulse frequency of TSH was higher (P < .05) on day 12 than on day 19, but both were similar to that on day 2. In Exp. 2, secretion of TSH in Holstein heifers was altered by administering (i.v.; one-half of the daily dose given twice daily) either phosphate-buffered saline (SAL; n = 6), propylthiouracil (PTU; 20 mg/100 kg body weight [BW]; n = 6), or T4 (1 mg/100 kg BW; n = 5) from day 4 until the next estrus. Duration of estrous cycles during and after treatments, percentages of heifers exhibiting estrus, BW, and average daily gain were unaffected by treatment. Concentrations of TSH were higher (P < .05) in the afternoon than in the morning and higher (P = .06) in PTU heifers than in T4 heifers. Treatment with T4 during the treatment estrous cycle and for up to 6 d into the next estrous cycle increased (P < .01) concentrations of T4 and T3 compared to SAL and PTU. Treatment with PTU during the treatment cycle increased concentrations of T4 (P < .05) and TSH (P = .06) compared to SAL. We conclude that TSH secretion was pulsatile, demonstrated a diurnal change, and varied inconsistently during the estrous cycle. Altering thyroid hormones and TSH secretion in heifers seemed to have no effect on estrous behavior or estrous cycles.

Animals↗