Showing papers on "Propylthiouracil published in 1968"
TL;DR: The present studies demonstrate that iodine depletion increases the sensitivity of the thyroid to the goitrogenic effects of thyrotropin, and may provide an explanation for the development of thyroid enlargement without requiring an increased level of circulating thyrotopin.
Abstract: The present studies demonstrate that iodine depletion increases the sensitivity of the thyroid to the goitrogenic effects of thyrotropin. Iodine depletion was induced by feeding rats a low iodine diet containing propylthiouracil for 10-14 days before hypophysectomy. Accumulation of iodine in the thyroid after hypophysectomy was prevented by continuing the antithyroid drugs in the diet. Doses of thyrotropin as low as 3 mU/100 g of body weight per day produced significant thyroid enlargement in 3-7 days in iodine-depleted rats. Adding propylthiouracil or perchlorate to the diet during treatment with thyrotropin did not reduce or augment the goitrogenic response to thyrotropin in iodine-depleted rats. Increasing the level of circulating iodide also did not reduce the goitrogenic response to thyrotropin. The increased sensitivity of the iodine-depleted thyroid gland may provide an explanation for the development of thyroid enlargement without requiring an increased level of circulating thyrotropin.
145 citations
TL;DR: Iodine deficiency results in at least as great an increase in the T3/T4 ratio of iodothyronines secreted as in those synthesized, which is an important adaptive mechanism in maintaining a euthyroid state in the face of inadequate iodine substrate.
Abstract: The relative proportion of total radioactivity secreted by the thyroid gland as triiodothyronine (T3) or as thyroxine (T4) in rats made iodine deficient to varying degrees was investigated using single-pass perfusion of 131I prelabeled thyroid glands in situ with nonradioactive blood. The T3/T4 ratio of the thyroid effluent increased progressively with the length of time rats were iodine deficient and averaged > 3 at 11 months. T3/T4 was almost invariably higher in the thyroid effluent than in the thyroid gland itself. No significant secretion of iodotyrosines was found, even in severely iodine-deficient rats. It is concluded that iodine deficiency results in at least as great an increase (and possibly greater) in the T3/T4 ratio of iodothyronines secreted as in those synthesized. This is an important adaptive mechanism in maintaining a euthyroid state in the face of inadequate iodine substrate. (Endocrinology 83: 1193, 1968)
86 citations
TL;DR: It is suggested that availability of thyroid hormone prior to birth and again after weaning age is reached, is not critical for development, possibly because other physiological factors operate to influence the rate of developmental processes.
77 citations
TL;DR: Pretreatment of male or female rats with a single injection of benzpyrene 48 hr before cannulation of the bile duct produced a 3- and 4-fold increase in billary excretion of exogenously administered or endogenously produced labeled thyroxine.
68 citations
TL;DR: Results indicate that the degree of incorporation of stable iodide into thyroids of rats on an adequate iodine intake is higher than previously thought.
Abstract: Work of previous investigators has established that the distribution of 131I among the iodoamino acids of the thyroids of rats on an adequate iodine intake is not seriously affected by a previous acute injection of NaC104, whereas it is markedly altered by acute administration of propylthiouracil (PTU). In iodinedeficient rats, we observed that the administration of NaC104 shortly before injection of carrierfree 131I resulted in a striking further increase in the usual high values for MIT*/DIT/, and in marked decreases in T4/ and T3/. Similar changes were seen after injection of PTU. The effect of NaC104 was completely abolished by administration of 20 /μg of stable iodide together with the 131I. Similarly, in iodine-deficient rats not receiving NaC104, injection of graded doses of iodide carrier (up to 5 μg) with 131I led to progressively greater values for T4/ and DIT/, and to progressively lower values for MIT/ and T3/. These results indicate that the degree of incorporation of stable iodide into thyro...
49 citations
TL;DR: It was concluded that 0.1, 0.15, and 0.2% thiouracil (TU) are equally effective in producing hypothyroid changes up to age 3 weeks, but PTU has a greater depressive effect on body weight because of its probably disagreeable taste and consequent effect upon food intake.
41 citations
Journal Article•
TL;DR: Data suggest that modifications of the carcinogenic response of rats to methylcholanthrene as a result of altered thyroid hormone levels were due principally to the growth-promoting stimulus of thyroid hormone, or lack of it, upon established neoplastic cells.
Abstract: The administration of thyroxin at a dosage of 2.5 µg per 100 gm body weight daily for 7 months, beginning 10 days before methylcholanthrene treatment was started, only slightly altered the carcinogenic response of rats to methylcholanthrene. Chronic administration of propylthiouracil during the same period significantly inhibited mammary cancer induction by methylcholanthrene. However, in rats initially made hypothyroid by propylthiouracil administration, but in which the thyroidal status was subsequently reversed by administration of thyroxin (2.5 µg per 100 gm body weight daily) beginning 10 days after cessation of carcinogen feedings, the incidence and latency of appearance of mammary cancer were not different from control rats treated with methylcholanthrene only. These data suggest that modifications of the carcinogenic response of rats to methylcholanthrene as a result of altered thyroid hormone levels were due principally to the growth-promoting stimulus of thyroid hormone, or lack of it, upon established neoplastic cells.
27 citations
TL;DR: The present study considers the rate of development of DMBA-induced breast cancer in rats made iodine deficient or hypothyroid and finds that the incidence of breast cancer is higher among women with Hypothyroidism and in those residing in regions where goitre is endemic.
Abstract: THE development of mammary tumours in rats by orally feeding the chemical carcinogen 7,12-dimethylbenz(a)-anthracene (DMBA) has been shown to be influenced by the hormonal state of the animal1. We previously observed that breast dysplasia could be induced in iodine deficient and propylthiouracil (PTU)-treated rats given oestrogen or testosterone2. Furthermore, the incidence of breast cancer is higher among women with hypothyroidism and in those residing in regions where goitre is endemic3. The present study considers the rate of development of DMBA-induced breast cancer in rats made iodine deficient or hypothyroid.
26 citations
01 Jan 1968
23 citations
TL;DR: After 20 days of treatment with propylthiouracil, a two-fold increase in the amount of β-glucuronidase per gram of rat thyroid was noted, and this change was manifested cytochemically by both an increase inThe number ofβ-glue containing granules and an enhancement of the generalized cytoplasmic activity.
Abstract: After 20 days of treatment with propylthiouracil, a two-fold increase in the amount of β-glucuronidase per gram of rat thyroid was noted. This change was manifested cytochemically by both an increase in the number of β-glucuronidase containing granules and an enhancement of the generalized cytoplasmic activity. The results are discussed in relation to the dual localization of β-glucuronidase.
19 citations
TL;DR: It is shown that ATZ, like PTU, not only interferes with organification of iodine but also inhibits the coupling of iodotyrosines to form iodothyronines.
Abstract: SummaryThe effects of 3-amino-1,2,-4-triazole (ATZ) on weight, content of iodine, and histology of the thyroid in rats were determined and compared to the effects of propylthiouracil (PTU), and KCIO4. In an 83-day period of treatment, ATZ and PTU produced goiters of comparable size. The KCIO4 treatment resulted in slightly greater depletion of iodine in the thyroid, smaller goiters, and less thyroxine depletion of the thyroid. The effect of ATZ treatment on intrathyroid metabolism of iodine in rats was studied and compared to similar studies in rats without treatment. In the ATZ-treated group, there was a progressive decrease in T3 and T4 and a slight increase in the proportion of MIT. The biologic half-life of 131I in the thyroid of the control and treated groups was 4.9 and 1.3 days, respectively. These findings are similar to those found previously for PTU and show that ATZ, like PTU, not only interferes with organification of iodine but also inhibits the coupling of iodotyrosines to form iodothyronines.
TL;DR: No significant effect of altered metabolic activity on anesthetic requirement could be demonstrated and MAC values tended to be temperature dependent, but the magnitudes of these changes were small and could be attributed to the effect of temperature on lipid solubility.
Abstract: The effects of acute drug-induced hypo- and hyperthyroidism on cyclopropane requirement (MAC) have been studied in rats. Animals treated with propylthiouracil and triiodothyronine showed marked alterations in basal metabolic rate. However, measurements of oxygen consumption in isolated nonstimulated brain slices showed no differences from control. No significant effect of altered metabolic activity on anesthetic requirement could be demonstrated. MAC values tended to be temperature dependent, but the magnitudes of these changes were small and could be attributed to the effect of temperature on lipid solubility.
TL;DR: Rats were force-fed a single dose of antithyroid compound and groups of animals were then injected with 131I at various times and killed 4 hr later and a slow decrease of thyroid activity to the initial level took place in most cases.
Abstract: Rats were force-fed a single dose of antithyroid compound (2, 4, 8 or 16 mg thiocyanate; 4 mg Tapazole; 4 mg propylthiouracil; 200 mg sulfathiazole; 16 mg perchlorate) at “0 hr.” In some cases a second (24 or 72 hr after the first one) or a third dose (144 hr after the first one) was administered. Groups of animals were then injected with 131I at various times and killed 4 hr later. A decrease of thyroid function was found which lasted for about 20 hr. After that a rebound period was observed which lasted for up to 100–150 hr. Finally, a slow decrease of thyroid activity to the initial level took place in most cases. The rebound period was not found to depend either on the chemical nature or on the dosage of the compound used. (Endocrinology 83: 1268, 1968)
TL;DR: The purpose of this paper is to report on the toxicity of several widely used antidepressant and tranquillizer drugs in mice made hyperthyroid by the addition of desiccated thyroid to the diet, and to draw attention to possible hazards in their use in thehyperthyroid state in man.
Abstract: It is evident from the literature that there is a relation between thyroid hormones and the toxicity of drugs and other chemical substances. The administration of thyroxine or desiccated thyroid to various animal species is reported to increase suscep tibility to the toxic effects of the following compounds: alloxan (Houssay and Sara, 1945), endotoxin (Kroneberg and Potzsch, 1952), cocaine, o-dinitrophenol, and dinitro-o-cresol (Glaubach and Pick, 1931, 1934), morphine (Hunt and Seidell, 1910), adrenaline (Kroneberg and Hilter, 1951), ephedrine (Halpern, Drudi-Baracco, and Bessirard, 1964), amphetamine (Moore, 1965), a non-hydrazide monoamine oxidase inhibitor (Carrier and Buday, 1961), and imipramine (Prange and Lipton, 1962). There is less evidence concerning the toxicity of drugs in the hypothyroid state; a search of the literature showed references to only two substances. The toxicity of imipramine was reported to be lower in mice in which thyroid function had been reduced by treatment with propylthiouracil (Prange, Lipton, and Love, 1963), though this was not confirmed by later studies (Prange, Lipton, and Love, 1964), and the toxicity of alloxan was reduced in thyroidectomized rats (Houssay and Sara, 1945). The purpose of this paper is to report on the toxicity of several widely used antidepressant and tranquillizer drugs in mice made hyperthyroid by the addition of desiccated thyroid to the diet, and to draw attention to possible hazards in their use in the hyperthyroid state in man.
TL;DR: Thyroid release of radioiodine was inhibited by excess iodide in rats receiving small daily dose of propylthiouracil (PTU) and demonstration of the iodide effect in thyroxine and TSH treated animals indicated further that the iodides effect was not due to inhibition of TSH secretion.
Abstract: Thyroid release of radioiodine was inhibited by excess iodide in rats receiving small daily dose of propylthiouracil (PTU). This inhibition by excess iodide is not due to the synthesis and release of unlabeled thyroid hormone in amounts adequate to inhibit the release of thyrotropin, for the dilution of 131I within the thyroid by newly formed organic iodine after excess iodide is the same in the groups which received either a small (5 rag) or a large (30 mg) dose of PTU. Furthermore, the amount of plasma PBI newly secreted is negligible at both levels of PTU. Demonstration of the iodide effect in thyroxine and TSH treated animals indicated further that the iodide effect was not due to inhibition of TSH secretion. Administration ofsmall dose of PTU immediately augmented release of radioiodine from the thyroid, increased blood TSH within 24 hr and produced a large goiter after 2 weeks. Large doses of PTU are less effective in these actions. Administration of a small dose of methimazole similarly augments th...
TL;DR: It is tentatively concluded that estrogen may have a dual action on the thyro‐pituitary axis: on one hand, a depressing influence on thyrotroph cells and on the other hand a direct stimulatory effect on the thyroid gland.
Abstract: The influence on pituitary cytology of propylthiouracil (PTU) and estradiol benzoate (EB) administered singly and in combination was studied by electron microscopy in adult female rats. PTU alone induced striking changes in the morphology of thyrotroph cells, which were all transformed into typical thyroidectomy cells, characterized by enormously dilated ergastoplasmic sacs; the acidophils were degranulated and some of them took the appearance of relatively quiescent prolactin cells rather than degranulated somatotrophs. EB alone caused no definite changes in the morphology of thyrotroph cells; its essential effect was the development of a large number of prolactin cells. When both treatments were combined, thyroidectomy cells were found, existing side by side with untransformed thyrotrophs and exhibiting less dilated ergastoplasmic sacs than after PTU alone; prolactin cells were present in great number and showed a more developed ergastoplasm than after EB alone. Thyroid weight and height of the follicular cells were not changed by EB given singly; they were both increased under the influence of PTU; thyroid weight but not mean height of the follicular cells was slightly less increased when EB was added to PTU. It is tentatively concluded that estrogen may have a dual action on the thyro-pituitary axis: on one hand, a depressing influence on thyrotroph cells and on the other hand a direct stimulatory effect on the thyroid gland.
TL;DR: The development of goiter in the presence of a high serum PBI cannot be explained by assuming that all 3 goitrogens interfered with the deiodination of thyroxine.
Abstract: Rats were fed propylthiouracil (0.05%), methimazole (0.05%), or sulfaguanidine (1%) and injected with graded doses of thyroxine (0.5–3.0 jug) daily for 2 weeks. In spite of the high serum PBI with doses of 1.0 and 1.5 μg of thyroxine, goiter was still observed in animals fed propylthiouracil. Goiter was prevented only when the PBI was increased to 2.2 times that of the control level by giving 2.0 μg of thyroxine. Similar effects were found with methimazole and sulfaguanidine. In animals which were thyroidectomized and given thyroxine, methimazole slightly elevated the serum PBI and reduced the urinary excretion of radioiodine after a single injection of labeled thyroxine. However, since sulfaguanidine was without effect in these respects, the development of goiter in the presence of a high serum PBI cannot be explained by assuming that all 3 goitrogens interfered with the deiodination of thyroxine. On the other hand,goiter was prevented in propylthiouracil-fed animals by doses of thyroid powder which resu...
TL;DR: Rat chromosomes prepared from thyroid cells grown in culture did not differ from those described for other tissues of this species in terms of incidence of abnormal chromosomes.
Abstract: Rat chromosomes prepared from thyroid cells grown in culture did not differ from those described for other tissues of this species. The incidence of thyroid cells with abnormal chromosomes was not increased by giving propylthiouracil to rats for 15 weeks. The thyroid chromosomes were damaged by injection of 1\\p=n-\\25 \\g=m\\cof 131I. The damage persisted in the unstimulated thyroid for 15 weeks. Administration of propylthiouracil to rats after 131I caused significant reduction in the frequency of thyroid cells with radiation-damaged chromo-
TL;DR: The observation of Alexander and Wolff that rats on 6-propyl-2-thiouracil (PTU) have larger goiters than those on KCIO4 is investigated, and there is a difference in the plasma insulin levels of animals on different goitrogens.
Abstract: We have investigated further the observation of Alexander and Wolff (1,2) that rats on 6-propyl-2-thiouracil (PTU) have larger goiters than those on KCIO4, and an intermediate one when both drugs are given simultaneously. We have confirmed their data regarding suppression of thyroid hormone secretion and plasma TSH activities. The latter were equally high in rats on PTU and KCIO4, at least from 6 days of treatment onward. Plasma TSH activities of rats on the mixed goitrogen diet were higher. Moreover, we have observed that there is a difference in the plasma insulin levels of animals on different goitrogens. It is normal in rats on PTU, and low in those on KCIO4. With the 2 goitrogens, insulin levels are initially comparable to those of rats on PTU alone, finally decreasing to levels comparable to those only on KCIO4. A correlationcorrelation coefficient with a high level of significance was found when the individual thyroid weights of all rats on goitrogens were plotted against the corresponding plasma i...
TL;DR: The effects of increasing or decreasing the endogenous secretion of thyroid-stimulating hormone on the iodinating activity of the rat thyroid gland were investigated and the activity began to rise on the fifth day after termination of thyroxine treatment.
Abstract: The effects of increasing or decreasing the endogenous secretion of thyroid-stimulating hormone on the iodinating activity of the rat thyroid gland were investigated. The thyroid iodinating activity of rats on 0.01% propylthiouracil in the drinking water increased linearly for 3 days and reached a maximum of 230 to 240% of the control on or about the fourth day of treatment. The daily injection of thyroxine (10 μg/100 g intraperitoneally) or hypophysectomy resulted in a rapid decrease in the iodinating activity between the first and second day, approaching a basal level by the third day. When the iodinating activity was suppressed for 4 days by daily injections of thyroxine, the activity began to rise on the fifth day after termination of thyroxine treatment.
TL;DR: Intestinal absorption of labeled thyroxine was lower in the groups fed Purina than in the group fed the Remington diet, and the serum PB131I of the former group was half that of the latter, which accounted for this trend of lowered serum PBI.
Abstract: Effects of diets on pituitarythyroid interplay were studied in the rat. Thyroxine, 2 μg ip daily, prevented goiter in rats fed a Remington diet containing propylthiouracil (0.05%). However, when the animals were fed Purina chow with propylthiouracil, 4.5 μg of thyroxine was required to prevent enlargement of the thyroid. Only when 4.5 ng thyroxine was administered did the serum PBI of the Purinafed group reach a value comparable to that of the Remington-fed group, which received 2 μg of thyroxine. Neither the iodine content of the diet nor the thyroxine-plasma protein interaction accounted for this trend of lowered serum PBI. Intestinal absorption of labeled thyroxine was lower in the groups fed Purina than in the group fed the Remington diet, and the serum PB131I of the former group was half that of the latter. The fecal loss of thyroxine was greater in the Purina-fed group than in the Remington-fed group when the animals were fed propylthiouracil and injected with stable and 131I-thyroxine. The serum PB...
TL;DR: It is likely that estrogens stimulate and goitrogens depress thyroidal iodide uptake by influencing directly the activity of thyroidal Nat, K+-activated ATPase.
Abstract: An ATPase preparation of cell membranes was obtained from pig thyroid gland and the effects of various thyroid-tropic substances on it were systematically studied in vitro. TSH had little effect in stimulating Na+, K+-activated ATPase even at very high concentrations. Physiologically active estrogens, 1715-estradiol, estriol and estrone, were found to stimulate the enzyme significantly even at extremely low concentrations. Progesterone was active only at high concentrations. Testosterone, cortisone, dexamethasone, iodide, iodotyrosines, iodothyronines and perchlorate were all without effect. Thiocyanate, thiourea, propylthiouracil and methylthiouracil were slightly, but consistently, effective in depressing the enzyme. It is likely that estrogens stimulate and goitrogens depress thyroidal iodide uptake by influencing directly the activity of thyroidal Nat, K+-activated ATPase.
TL;DR: Thyroid lobes from intact and hypophysectomized rats fed an iodine-deficient or high-iodine diet were incubated with carrierfree 131I- in graded concentrations of PTU, confirming many previous in vivo and in vitro studies and suggesting that this differential effect ofPTU might be due to some alteration in the structure of thyroid protein produced by Hypophysectomy.
Abstract: Thyroid lobes from intact and hypophysectomized rats fed an iodine-deficient or high-iodine diet were incubated with carrierfree 131I- in graded concentrations of PTU. In the lobes from intact rats there was a negative correlation of the DIT/MIT ratio with concentration of PTU, confirming many previous in vivo and in vitro studies. In contrast, in the lobes from hypophysectomized rats there was no significant correlation of DIT/MIT ratio with PTU concentration. These observations are similar tothose made previously in vivo and establish that the qualitative difference in the effect of PTU on the DIT/MIT ratio in intact compared to hypophysectomized rats is not due to a difference in the extrathyroidal metabolism of PTU in these 2 types of animals. It is suggested that this differential effect of PTU might be due to some alteration in the structure of thyroid protein produced by hypophysectomy. (Endocrinology 83: 592, 1968)
Journal Article•
TL;DR: In kurzdauernden Versuchen wird gezeigt, dass Propylthiouracil, das sonst als Thyreostaticum bei Hyperthyreose gebraucht wird, die Jodidausscheidung durch die Niere erhöht.
Abstract: In kurzdauernden Versuchen wird gezeigt, dass Propylthiouracil, das sonst als Thyreostaticum bei Hyperthyreose gebraucht wird, die Jodidausscheidung durch die Niere erhoht. Die Erhohung der Jodidausscheidung ist mit der ebenfalls auftretenden Steigerung der Ausscheidung von Chlorid, Natrium und Kalium korreliert, ohne dass Wasser in vermehrtem Masse ausgeschieden wird.
TL;DR: Recovery of thyroid function after withdrawal of the antithyroid agents was markedly affected by the iodide supplementation.
Abstract: Iodide-deficient female rats were fed propylthiouracil (PTU) or dl-5-vinyl-oxazolidinethione mixed into a low-iodide diet for 10 days and then were either maintained on a low-iodide diet or given iodide supplements. Recovery of thyroid function after withdrawal of the antithyroid agents was markedly affected by the iodide supplementation. Without the iodide supplement 1) there was no regression of goiter or increase in serum PBI concentration; 2) the uptake of 131I by the thyroid was rapid and the 4-hr uptakes showed the expected ‘rebound’ phenomenon; 3) the 131I which was accumulatedby the 4th hr after administration was rapidly lost from the gland so that the 24-hr values were low and did not show the “rebound” phenomenon; 4) the ratios of radioactive DIT%MIT and T4%T3 were reversed; 5) there was a rapid loss of 131I-labeled MIT and DIT from the thyroid between the 4th and 24th hr after isotope administration, commencing 1 day after withdrawal of the drug, and a rapid loss of radioactive T4 and T3, comm...