Showing papers on "Propylthiouracil published in 1982"
TL;DR: Evidence was obtained for the existence of two thiol-dependent 5'-deiodinase entities that predominates in tissue from euthyroid and long-term hypothyroid rats, and one of these follows "ping-pong" kinetics with dithiothreitol as the cosubstrate, and is inhibited by propylthiouracil (PrSUra) and iodoacetate.
Abstract: Enzymatic 5'-deiodination of 3,3',5'-triiodothyronine (rT3) and 3,3',5,5'-tetraiodothyronine (thyroxine, T4) was studied in microsomal preparations of rat cerebral cortex. Evidence was obtained for the existence of two thiol-dependent 5'-deiodinase entities. One of these predominates in tissue from euthyroid and long-term hypothyroid rats, is specific for rT3, follows "ping-pong" kinetics with dithiothreitol as the cosubstrate, and is inhibited by propylthiouracil (PrSUra) and iodoacetate. Inhibition by PrSUra is uncompetitive with rT3 and competitive with dithiothreitol. These properties are shared with the 5'-deiodinase activity of liver and kidney. The activity of a second type of 5'-deiodinase is highest in cerebral cortex from short-term hypothyroid rats, prefers T4 to rT3 as the substrate, is insensitive to PrSUra and iodoacetate, and follows "sequential" reaction kinetics. A similar PrSUra-insensitive 5'-deiodinase activity is also found in pituitary but is not detectable in liver and kidney; it seems, therefore, characteristic of tissues in which local T4 to 3,3',5-triiodothyronine (T3) conversion supplies a major portion of the total intracellular T3.
246 citations
TL;DR: Propylthiouracil treatment did not reduce the frequency and incidence of complications in alcoholic hepatitis, but induced hypothyroidism in 4 patients and produced no beneficial effect on any of the hepatic biochemical tests.
112 citations
TL;DR: The relation between thyroid function and factor-VIII-related properties in both hypothyroid and hyperthyroid patients is discussed and significant increases were noted in factor VIII coagulant activity, factors-V III-related antigens, and ristocetin cofactor activity.
Abstract: Plasma factor VIII coagulant activity is decreased in hypothyroid patients and increased in hyperthyroid patients. We studied 21 untreated hypothyroid patients. Factor VIII coagulant activity was mildly decreased in association with significant depression of factor-VIII-related antigen and ristocetin cofactor activity in five patients. Factor-VIII-related properties significantly increased with oral thyroid replacement therapy in seven of 10 patients. Twenty-two untreated hyperthyroid patients were similarly evaluated. In 21 of these patients significant increases were noted in factor VIII coagulant activity, factor-VIII-related antigens, and ristocetin cofactor activity. Elevated factor-VIII-related properties returned to normal in all of 10 patients treated with radioactive iodine or propylthiouracil. We discuss the relation between thyroid function and factor-VIII-related properties in both hypothyroid and hyperthyroid patients.
108 citations
TL;DR: Propylthiouracil (PTU) levels in serum have been measured by RIA in five normal volunteers and four patients with untreated Graves' disease and there was a highly significant correlation between serum PTU levels and perchlorate-dischargeable iodide in both normals.
Abstract: Propylthiouracil (PTU) levels in serum have been measured by RIA in five normal volunteers and four patients with untreated Graves' disease. Peak PTU levels after 50, 200, and 300 mg PTU were 0.91 ± 0.13, 2.9 ± 0.6, and 4.0 ± 0.6 jug/ml in the normal subjects and 1.04 ± 0.1, 4.5 ± 0.7, and 7.1 ± 0.4 jug/ml in the hyperthyroid patients, respectively. Peak PTU levels and PTU area under the curve were significantly greater at the 300-mg dose (P < 0.01) in the hyperthyroid patients compared to the normal subjects. The effect of PTU on iodide organification was assessed by perchlorate discharge testing. Both the normals and the hyperthyroid patients had normal basal perchlorate-dischargeable 123I. Four hours after an oral dose of PTU, the hyperthyroid patients had a greater percentage of perchlorate-dischargeable 123I than the euthyroid controls (+38 ± 5% vs. +13 ± 2% P < 0.02). There was a highly significant correlation between serum PTU levels and perchlorate-dischargeable iodide in both normals (r = 0.86; P...
61 citations
TL;DR: It appeared that loss of thyroid tissue, rather than the hypothyroidism per se, was responsible for the decrease in progression of the exophthalmos, which is related to effects of propylthiouracil on the immune system.
Abstract: Patients with both exophthalmos and hyperthyroidism were treated with different modes of therapy for their hyperthyroidism. Propylthiouracil followed by surgery, propylthiouracil followed by radioactive iodine, propylthiouracil alone, and radioactive iodine alone were used. Some of the patients became hypothyroid and were made euthyroid with levothyroxine sodium. Based on the mode of therapy and whether or not hypothyroidism occurred, each patient was assigned to one of seven groups and followed up for 18 months or longer. Careful exophthalmometry was performed at six-week intervals in all patients. Though progression of exophthalmos was noted in all groups, the group that received propylthiouracil demonstrated the greatest progression of exophthalmos. In the group receiving sodium iodide I 131 therapy and in the group treated surgically, the rate of progression of exophthalmos was lessened with the development of hypothyroidism. Since these hypothyroid patients were made euthyroid with supplemental levothyroxine, it appeared that loss of thyroid tissue, rather than the hypothyroidism per se, was responsible for the decrease in progression of the exophthalmos. The continued progression of exophthalmos in the propylthiouracil-treated group may be related to effects of propylthiouracil on the immune system. ( JAMA 1982;247:2135-2138)
60 citations
TL;DR: It is concluded that a normal thyroidal state is required to evoKe the swift increase in alcohol metabolism (SIAM) and an elevation of oxygen consumption.
51 citations
TL;DR: In a large population of euthyroid, hypothyroid, and hyperthyroid rats there was a linear correlation between serum TSH and the ratio in the hypothalamus of the concentration of 5- hydroxyindoleacetic acid (5-HIAA) to 5-HT.
Abstract: The aim of this study was to determine the specific roles of hypothalamic dopamine (DA), norepinephrine (NE), and serotonin (5-HT) in controlling the release of TSH in hypothyroid and euthyroid states in the rat. Selected ion monitoring (computerized gas chromatography/mass spectrometry) was used to assay, simultaneously, medial basal hypothalamic concentrations of DA, NE, and 5-HT and their major metabolites. The turnover of each amine in the hypothalamus of individual animals was estimated from the ratio of the concentration of metabolite to that of its precursor amine. In hypothyroid rats an increase in 5-HT turnover at various times after propylthiouracil (PTU) induction of hypothyroidism was associated with the expected rise in TSH secretion. In a large population (n = 90) of euthyroid, hypothyroid, and hyperthyroid rats there was a linear correlation between serum TSH and the ratio in the hypothalamus of the concentration of 5- hydroxyindoleacetic acid (5-HIAA) to 5-HT. The hypothesis that high hypo...
50 citations
TL;DR: The results indicate that even mild hypothyroidism during early postnatal development causes permanent impairment of brain function, which manifests itself in part by an altered brain content of IR-SRIF.
Abstract: The contents of immunoreactive somatostatin (IR-SRIF) and β-endorphin (IR-β-EP) in 12 brain regions were examined in rats exposed neonatally to propylthiouracil (PTU) through the mother's milk. Since the dose of PTU used in this study is lower than the usual dose employed to induce hypothyroidism, a milder form of neonatal hypothyroidism resulted. This conclusion is supported by the only mild subnormal growth of rats to adulthood and serum T4 and T3 concentrations in the normal range. Adult rats treated with PTU neonatally had significantly higher IR-SRIF contents in several brain regions compared to controls, whereas IR-β-EP levels were not significantly different (significant increase only in the thalamus) in most regions. The results indicate that even mild hypothyroidism during early postnatal development causes permanent impairment of brain function, which manifests itself in part by an altered brain content of IR-SRIF.
43 citations
TL;DR: Data are compatible with the hypothesis that NH leads to a permanent resetting of the regulatory set-point for pituitary TSH secretion and to increased sensitivity to the feedback inhibitory effects of thyroid hormones.
Abstract: The acute and latent effects of neonatal hyperthyroidism (NH) on the hypothalamic-pituitary-thyroid axis were studied in the rat after treatment of newborn animals with L-T4 (0.4 μg/g BW, daily) for a period of 12 days. NH was associated with a permanent reduction in body weight in both male and female rats, in addition to a delay in the attainment of peak concentrations of hypothalamic TRH and pituitary and serum TSH. Serum TSH, T4, and T3 concentrations also were significantly and permanently reduced in NH animals (P < 0.01) after cessation of L-T4 treatment. The serum TSH secretory response to 1 μg synthetic TRH also was evaluated in 120-day-old control and NH rats, before and after the administration of L-T4 (0.6 μg/100 g BW for 7 days) or propylthiouracil (0.05% in the drinking water for 14 days). In the baseline state, adult NH rats had a net secretory response similar to that of controls (189.0 ± 31.3 vs. 227.0 ± 29.3 μg/ml-min). Administration of T4 significantly decreased while propylthiouracil t...
40 citations
TL;DR: Five patients were found who had seven episodes of SRH while receiving thyroid hormone suppression therapy after having verified chronic LT and LT-SRH, indicating that thyroid suppression with thyroid hormone may be ineffective in preventing this disease.
Abstract: • The duration of the hyperthyroidism associated with lymphocytic thyroiditis (LT) with spontaneously resolving hyperthyroidism (SRH) was serially monitored in groups of patients who were not given any treatment (control subjects) or treated with propylthiouracil and/or propranolol hydrochloride and prednisone. The length of time for the thyroxine tests from diagnosis to the normal range was 57 ± 17, 45 ± 13, and 15 ± 7 days (mean ± SD) indicating a dramatic response to prednisone therapy but none to propylthiouracil and/or propranolol therapy. Five patients were found who had seven episodes of SRH while receiving thyroid hormone suppression therapy after having verified chronic LT (two patients) and LT-SRH (three patients). This indicates that thyroid suppression with thyroid hormone may be ineffective in preventing this disease. Two patients were treated by subtotal thyroidectomy because of recurrent or prolonged episodes of SRH. From this experience, the therapeutic alternatives available to the clinician are reviewed.
39 citations
TL;DR: Observations suggest that glucocorticoids play an important role in triggering lung cytodifferentiation during the third postnatal week in the rat, and that preconditioning of the lung by thyroid hormone optimizes this developmental effect of glucoc Corticoids.
Abstract: Between the 4th and 10th days of postnatal life in the rat, serum corticosterone levels were low and basal, while the rate of [3H]thymidine incorporation into lung DNA was maximal. From day 13, serum corticosterone levels began to rise significantly, and the lung [3H]thymidine incorporation rate began to fall dramatically; however, these events were obtunded by propylthiouracil-induced hypothyroidism. When 6- to 8-dayold euthyroid pups were given a single sc injection of 10 μg dexamethasone, the rate of DNA synthesis in the lung fell by 96.7% of the initial rate at 24 h. This steroidal effect was blunted in hypothyroid pups and restored by exogenous thyroid hormone. The thyroid status of the pup did not modify the response patterns of lung phosphodiesterase and cytosolic glucocorticoid receptor levels to dexamethasone treatment, although both parameters were influenced by thyroid hormone availability. Radiocholine incorporation into lung phospholipids, which was altered in hypothyroidism, was unaffected b...
TL;DR: The canine thyroid contained T4 deiodinases very similar to those of a peripheral thyroid hormone target organ, the liver, which are probably responsible for the relatively high secretion of T3 and rT3 compared to that of T4 found in previous studies.
Abstract: In previous studies using perfused dog thyroids we have found evidence for a modulation of thyroid secretion by intrathyroidal thyroxine deiodinases. The purpose of the present study was to examine in detail the in vitro characteristics of thyroidal 5- and 5′-deiodinases of T4and to make a comparison to T4 deiodinases from liver tissue. The sources of deiodinases were crude microsomal fractions prepared from thyroid and liver tissues obtained from the same dogs. Deiodinases from the two tissues behaved very similarly with respect to the time course of T3 and rT3 generation, dependency on the amount of added microsomes and substrate, and influence of temperature, pH, dithiothreitol, propylthiouracil, methimazol, ipodate, and added rT3. At pH 7.4, both T3 and rT3 were stable when added to the microsomal preparations. The apparent kinetic constants estimated from Lineweaver-Burk plots of T4 deiodination to T3 and rT3 by liver and thyroid microsomes, were similar for all reactions, (kinetic constant, 6.1-25.1...
TL;DR: A case of fulminant hepatitis that was probably caused by propylthiouracil therapy is reported, the first such fatal case reported, although death due to agranulocytosis after Propylthaviouracil administration has been previously described.
Abstract: To the Editor. —We would like to report a case of fulminant hepatitis that was probably caused by propylthiouracil therapy. To our knowledge, this is the first such fatal case reported, although death due to agranulocytosis after propylthiouracil administration has been previously described.1 Report of a Case. —A 20-year-old woman was in excellent health until the diagnosis of Graves' disease was made. Her condition was characterized by profound exophthalmos, a triiodothyronine uptake of 64% (normal, 22% to 34%), a thryoxine radioimmunoassay of 28.5 μg/dL (normal, 5 to 11 μg/dL), and a free thyroxine index of 18.2 (normal, 0.8 to 2.3). Subsequently, administration of 100 mg of propylthiouracil three times a day was instituted. Two weeks after therapy began, she experienced malaise and jaundice associated with abnormal findings from liver function tests. Laboratory values were as follows: SGOT, 750 IU/L (normal, 0 to 41 IU/L); alkaline phosphatase, 248 IU/L (normal,
Journal Article•
TL;DR: An association of granulocytopenia, eosinophilia, skin reaction and hepatitis during propylthiouracil (PTU) therapy for thyrotoxicosis in a 47 year old black female is reported.
Abstract: An association of granulocytopenia, eosinophilia, skin reaction and hepatitis during propylthiouracil (PTU) therapy for thyrotoxicosis in a 47 year old black female is reported. Clinical and biochemical abnormalities disappeared soon after discontinuation of PTU. That the drug was directly responsible for the observed complications is suggested by the clinical course and by in vitro lymphocyte transformation studies. The latter revealed sensitization to PTU during the acute phase of the disease, which was greatly reduced 5 weeks after discontinuation of the drug and was completely absent after 5 months.
TL;DR: It is suggested that there is not necessarily any close correlation between T3 release and cAMP release into perifusates of the rat thyroid, and that TSH and IBMX enhance T 3 release, but only IBMX increases cAMPRelease.
Abstract: We have established a perifusion system using rat thyroid. With this system, we analyzed the effects of TSH, 3-isobutyl-1-methylxanthine (IBMX) and iodide on the release of T3 and of cAMP, paying special attention to the relation between the release of the two substances. During perifusion, which was continued for 7 h, T3 release increased progressively with time and in a dose-related manner when TSH was added at concentrations of 0.1-10 mU/ml. However, cAMP release was unappreciable even in the presence of 10 mU/ml TSH. The release of T3 and cAMP was markedly enhanced by 3 x 10(-4) M IBMX. When iodide was added, a marked increase in cAMP release was unexpectedly observed. However, a slight but significant suppression of TSH-stimulated T3 release was shown with 1 x 10(-3) M iodide. TSH-stimulated T3 release was almost completely inhibited by 1 x 10(-3) M 6-n-propyl-2-thiouracil, but such a complete inhibition did not occur with 2-mercapto-1-methylimidazole. The cAMP release stimulated by IBMX was not affected by 6-n-propyl-2-thiouracil, but that stimulated by iodide was effectively inhibited. The present studies indicate that TSH and IBMX enhance T3 release, but only IBMX increases cAMP release. Iodide also results in a marked increase in cAMP release but does not affect T3 release from unstimulated thyroid and inhibits T3 release from TSH-stimulated thyroid. We suggest that there is not necessarily any close correlation between T3 release and cAMP release into perifusates of the rat thyroid.
TL;DR: 2,3-DHP represents a new class of antithyroid drug and its main action appears to be inhibition of peroxidase-catalyzed thyroid hormone formation in the thyroid gland.
Abstract: The antithyroid effect of 2,3-dihydroxypyridine (2,3-DHP) was investigated in vivo and in vitro. Thyroid studies were carried out on two groups of rats; one group of 14 rats were fed a low-iodine diet containing 1% 2,3-DHP for 25 days, and a control group of 12 rats received low-iodine diet alone. 2,3-DHP-treated rats had reduced thyroid function with a significant rise in serum thyrotropin (TSH) levels and decreased serum triiodothyronine (T3) levels; thyroxine (T4) and T3 contents of the thyroid gland were 20 and 10%, respectively, lower than those of controls. In vitro, 2,3-DHP inhibited peroxidase activity, and its antiperoxidase potency was similar to the commonly used thioureylene antithyroid drug, propylthiouracil. In addition, 2,3-DHP was a much weaker inhibitor of the thyroid conversion of T4 to T3 in vitro than propylthiouracil. 2,3-DHP represents a new class of antithyroid drug and its main action appears to be inhibition of peroxidase-catalyzed thyroid hormone formation in the thyroid ...
TL;DR: Effects of thyroid hormone on the development of neuromuscular junctions were investigated electrophysiologically in the diaphragms (sternal region) of normal, hypo‐ and hyperthyroid rats from the age of birth to day 35.
Abstract: 1. Effects of thyroid hormone on the development of neuromuscular junctions (n.m.j.s.) were investigated electrophysiologically in the diaphragms (sternal region) of normal, hypo- and hyperthyroid rats from the age of birth (day 0) to day 35.
2. Hypothyroidism in new-born rats was induced either by daily administration of propylthiouracil to mothers or by subcutaneous injection of 150 μCi 131I on day 1. Hyperthyroidism was induced by daily injection of thyroxine.
3. In normal rats up to day 10, muscle fibres were innervated polyneuronally. By day 20, multiple innervation was eliminated and muscle fibres received only a single input. In hypothyroid rats elimination of polyneuronal innervation was retarded by 5-8 days, while in hyperthyroid rats the elimination was accelerated by 2-3 days.
4. The frequency of miniature end-plate potentials (m.e.p.p.s) in normal rats increased from one per 40 sec on days 0-5 to 1/sec on days 25-35. The m.e.p.p. frequency in hypothyroid rats was 25-65% of that in normal rats of the same age. In hyperthyroid rats the m.e.p.p. frequency was normal up to day 18 but subnormal afterwards. The duration of m.e.p.p. measured on day 22-23 was slower in hypothyroid rats and faster in hyperthyroid rats, relative to m.e.p.ps in normal rats.
5. The sensitivity to acetylcholine (ACh) at extrajunctional regions in normal rats was about 100 mV/nC at birth and declined to 1 mV/nC by day 26. In hypothyroid rats, the ACh sensitivity was as high as 30 mV/nC on day 26; in hyperthyroid rats, ACh sensitivity on day 26 was undetectable.
6. With pairs of nerve stimuli (applied at a 50 msec interval), the second end-plate potential was facilitated until day 10 and depressed after day 16 in normal rats. This shift from facilitation to depression during development was not altered in either hypo-or hyperthyroid rats.
7. It is concluded that the lack and excess of thyroid hormone retards and facilitates the development of n.m.j.s. respectively. Possible mechanisms for this altered development are discussed.
TL;DR: It is concluded that alpha 1- and beta-adrenergic receptors are modulated by thyroid hormone in developmental as well as mature stages of the rat.
Journal Article•
TL;DR: 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.
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.
TL;DR: The effects of thyroid status on various aspects of hepatic lipid metabolism reported from this laboratory may, in part, have resulted from alterations in hepatic cAMP concentrations that changed in the Km for cAMP with little change in the Vmax.
Abstract: The effects of thyroid status on the activity of hepatic cAMP phosphodiesterase (PDE) were studied in the rat. Male rats were rendered hyperthyroid by treatment with T3 or hypothyroid by treatment with propylthiouracil. The hepatic particulate low Km PDE was solubilized, and its activity was measured at concentrations of 0.12–1.3 μM cAMP. The Km decreased in hypothyroidism and tended to increase in hyperthyroidism with respect to individual controls. The maximal velocity (Vmax) was unaffected by changes in thyroid status. The increases in Km correlated with increasing plasma T3, whereas the Vmax did not. Concentrations of cAMP increased in the livers from hyperthyroid rats and decreased in those from hypothyroid, in comparison with euthyroid rat livers. The effects of thyroid status on various aspects of hepatic lipid metabolism reported from this laboratory may, in part, have resulted from alterations in hepatic cAMP concentrations. These alterations, may have resulted secondarily from changes in the act...
TL;DR: It is concluded that thyroid hormones or thyroid dependent factors enhance pulmonary β-adrenergic receptor synthesis and that thyroid hormone is required for the normal postnatal maturation of the β- adrenergic receptors system in the rat lung.
Abstract: Beta-Adrenergic receptors were identified in membrane fractions of rat lung with the beta-adrenergic antagonists (-)-[3H]-dihydroalprenolol (-)-[3H]DHA) and (+/-)-[125I]-iodohydroxybenzylpindolol ((+/-)-[125I]HYP). Binding capacity (Bmax) for (-)-[3H]DHA increased progressively from 46 +/- 7 on day 18 of gestation to 510 +/- 70 femtomoles . mg-1 protein (mean +/- S.D.) on postnatal day 28, at which time adult Bmax was attained. An increase in (-)-[3H]DHA binding capacity of the lung was observed between postnatal days 15 and 28, during the known period of increased thyroid gland secretory activity, serum triiodothyronine (T3), and thyroxine (T4) concentrations in the rat. We therefore studied lung beta-adrenergic receptors in rat pups made hypothyroid with propylthiouracil (PTU) (in utero and postnatally) compared to normal age-matched control pups and to euthyroid pups which were treated with PTU but were also injected daily with thyroxine (T4-treated). Hypothyroid pups grew nearly normally until postnatal day 15 but grew poorly thereafter; but day 28 somatic and lung weight, lung DNA, and protein were markedly decreased in hypothyroid pups as compared to controls. Pulmonary beta-adrenergic receptors were similar in hypothyroid pups and controls on day 15, but were markedly decreased in hypothyroid pups on day 28 (294 +/- 57 versus 489 +/- 82 femtomoles . mg-1 protein in T4 treated euthyroid controls). Treatment of the hypothyroid pups with T4 on day 25 significantly increased lung beta-adrenergic receptors to near normal concentrations by day 28. We conclude that thyroid hormones or thyroid dependent factors enhance pulmonary beta-adrenergic receptor synthesis and that thyroid hormone is required for the normal postnatal maturation of the beta-adrenergic receptor system in the rat lung.
TL;DR: It is suggested that thyroid hormones increased SMG EGF synthesis by inducing cytodifferentiation in immature and mature mouse submaxillary gland (SMG) and increase SMG concentrations of nerve growth factor and epidermal growth factor (EGF).
Abstract: Previous studies have shown that thyroid hormones induced cytodifferentiation in immature and mature mouse submaxillary gland (SMG) and increase SMG concentrations of nerve growth factor and epidermal growth factor (EGF). These observations suggested that thyroid hormones increased SMG EGF synthesis. The following experiments were performed in order to determine the presence of specific nuclear T3 receptors in mouse SMG and the time and dose dependency of the SMG EGF response to a single injection of T3. In the first series of experiments, the presence of specific nuclear T3 receptors was established. The Ka of the receptor in SMG [0.60 ± 0.04 × 1010 M1 (mean ± SEM)] was similar to that observed in liver. The number of binding sites in SMG (46 ± 1 fmol/mg protein) was significantly less than in liver (266 ± 40 fmol/mg protein; P < 0.001). Induction of hypothyroidism in adult female mice by the administration of 0.1% propylthiouracil in their drinking water, led to a significant increase in the number of T...
TL;DR: Inhibition of thyroid function in neonatal rat pups by combined pre- and postnatal propylthiouracil treatment abolished the developmental rise in pulmonary glucocorticoid receptor levels.
Abstract: In the early postnatal rat, the level of glucocorticoid receptors in the lung increases during the first week of life (5) when thyroid hormone ontogenesis occurs (6). Inhibition of thyroid function in neonatal rat pups by combined pre- and postnatal propylthiouracil treatment abolished the developmental rise in pulmonary glucocorticoid receptor levels. A single injection of 1 μg T3 to these pups caused an elevation in receptor concentration to euthyroid values in 48 h. These findings support the hypothesis that thyroid hormone promotes tissue receptivity to glucocorticoids in the developing lung of the infant rat.
TL;DR: During the first 2 weeks of postnatal life in the rat, the activities of phosphodiesterase and guanylate cyclase in the lung were found to undergo significant age-related changes, and these changes coincided with the pattern of developmental changes in circulating thyroid hormone levels.
Abstract: During the first 2 weeks of postnatal life in the rat, the activities of phosphodiesterase and guanylate cyclase in the lung were found to undergo significant age-related changes. Low constant levels of these enzyme activities during the first 4 postnatal days were followed by a substantial increase to peak levels which plateaued between days 11 and 21 of age, and these changes coincided with the pattern of developmental changes in circulating thyroid hormone levels. When pups were rendered hypothyroid by combined pre- and postnatal treatment with propylthiouracil, the ontogenetic pattern of lung phosphodiesterase was abolished, as were those of serum thyroid hormones; however, that of lung guanylate cyclase was still evident, although slightly depressed. In contrast, treatment of euthyroid pups from the first day of life with daily injections of 1 μg T3 resulted in an advancement of lung phosphodiesterase ontogenesis, whereas that of guanylate cyclase was unaffected. A comparison between euthyroid and hy...
TL;DR: It is demonstrated that in NMU-treated rats: (1) slight hypothyroidism favors development of mammary and lung tumors, (2) severe hypothy thyroidism produces the opposite effect together with weight loss, and (3) the combination of PTU treatment and the carcinogen is followed by malignant thyroid tumors.
Abstract: Female rats were injected with the mammary gland carcinogen N-nitrosomethylurea (NMU) and were made hypothyroid by treatment with either propylthiouracil (PTU) or 131I. NMU (25–100 mg/kg) itself caused a dose-related increase in serum thyroxine levels. PTU (1.0–3.0 mg/100 ml of drinking water) caused a decrease in serum thyroxine and triiodothyronine levels in NMU-treated rats. At 28–31 weeks after injection of NMU alone, 9/43 rats (21%) had malignant mammary tumors. This incidence was increased to 11/30 (37% P > 0.1) and 13/30 (43% P P > 0.05) and caused a 33% decrease in final body weight. Treatment with 10 μCi of 131I gave a small decrease in serum thyroxine levels in NMU-treated rats and increased the incidence of malignant mammary tumors to 11/26 rats (42%, 0.1 > P > 0.05). In addition, PTU (0.3 mg/100 ml) plus NMU induced ...
TL;DR: The data support the earlier observations that modulation of intestinal calcium transport by phosphorus is not entirely mediated by vitamin D and suggest that hypophosphatemic stimulation ofestinal calcium transport is mediated by a hypophyseal factor indpendent of vitamin D.
Journal Article•
TL;DR: A good correlation between T3 serum levels and PRA was found, but there was no such correlation between H2O levels and T4 serum levels, and the basal levels of angiotensin I and plasma renin activity increased, were not altered by T4 and decreased after PTU administration.
Abstract: The basal levels of angiotensin I and kinetic parameters of renin-angiotensin system were studied under control, hyper- and hypothyroidism conditions. The serum levels of triiodothyronine (T3) and thyroxine (T4) and plasma angiotensin II have been measured radioimmunoassay. Hyperthyroidism was induced by 5.5 micrograms/200 g of T3 or 100 micrograms/200 g of T4 administration for 12 days, and hypothyroidism by propylthiouracil (PTU) administration of 1 mg/200 g for 12 days. Basal levels of angiotensin I and plasma renin activity (PRA) increased after T3 injection, were not altered by T4 and decreased after PTU administration. T3 and T4 induced an increase in plasma renin concentration (PRC), while PTU induced a decrease in PRC. Plasma renin substrate (PRS) decreased in hyperthyroid rats and was unchanged by experimentally induced hypothyroidism. A good correlation between T3 serum levels and PRA was found, but there was no such correlation between T4 serum levels and PRA.