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Showing papers on "Propylthiouracil published in 1980"


Journal ArticleDOI
TL;DR: Adult seizure-susceptible rats showed increased sensitivity to audiogenic seizures when they were fed propylthiouracil, the most potent goitrogen.
Abstract: The feeding of goitrogens during pregnancy and lactation causes the offspring of rats to be partially deaf and persistently sensitive to audiogenic seizures. The most potent goitrogen, propylthiouracil, caused severe dysfunction and disorganization of the organ of Corti. Adult seizure-susceptible rats showed increased sensitivity to audiogenic seizures when they were fed propylthiouracil.

89 citations


Journal ArticleDOI
01 Feb 1980-JAMA
TL;DR: A patient had cutaneous vasculitis, leukopenia, and splenomegaly caused by the antithyroid drug, propylthiouracil, and direct immunofluorescence studies demonstrated IgM and C3 of the vessel walls suggesting immune complex deposition.
Abstract: A patient had cutaneous vasculitis, leukopenia, and splenomegaly caused by the antithyroid drug, propylthiouracil. Histopathologic changes of acute vasculitis of the superficial and deep dermal blood vessels accompanied by fibrin thrombi formation were found in biopsy specimens of the cutaneous lesions. Direct immunofluorescence studies demonstrated IgM and C3 of the vessel walls suggesting immune complex deposition. The literature disclosed five cases with similar features associated with propylthiouracil therapy. Characteristic cutaneous findings include a recurrent, self-limited, symmetrical purpuric eruption that can involve the face or earlobes. Clinicians should recognize these changes as a cutaneous sign of a vasculitis associated with propylthiouracil therapy. ( JAMA 243:458-461, 1980)

52 citations


Journal ArticleDOI
TL;DR: The formation of a reversible PTU-enzyme complex was found to protect T4 5′-deiodination from irreversible inactivation by iodoacetate or N-ethylmaleimide.
Abstract: T4 5′-deiodinase, found in cell membranes of kidney and liver, is a thiol-dependent enzyme inhibited by propylthiouracil (PTU). Pretreatment of enzymatically active kidney membrane preparations (Mx) with PTU (10 μm) and increasing concentrations of L-T4 under N2 resulted in increasing degrees of persistent inhibition, as assayed in the absence of pretreatment reagents. Aerobic pretreatment with PTU in the presence or absence of L-T4 resulted in 80% inhibition of T4 5′-deiodination. Sulfhydryl modification of kidney Mx with iodoacetate or Nethylmaleimide irreversibly inactivated T4 5′-deiodinase. The formation of a reversible PTU-enzyme complex was found to protect T4 5′-deiodination from irreversible inactivation by iodoacetate or N-ethylmaleimide. A dose-dependent increase in the 35S content of kidney Mx was found after injection of [35S]thiouracil (TU) into rats, and the Mx 35S content was reduced 4-fold by simultaneous injection of methimazole. Treatment of kidney Mx, containing bound ;ISS, with 10 mm ...

47 citations


Journal ArticleDOI
TL;DR: It is indicated that thyroid hormones increase NGF content and concentration in the submaxillary gland and liver of adult male mice and are suggestive of increased NGF synthesis, which may play an important regulatory role in NGF metabolism in peripheral tissues of the adult mouse.

40 citations


Journal ArticleDOI
TL;DR: It appears that, in man, methimazoles is the most active of antithyroid agents currently available, that carbimazole is essentially inactive per se but is bioactivated to methimzole, and that carbIMazole offers neither dynamic nor kinetic advantages over methimZole.
Abstract: The in vitro effects of equimolar concentrations (0.1, 0.33 and 1.0 mmol/l) of carbimazole, methimazole, propylthiouracil and propranolol on thyroid peroxidase activity were studied on thyroid tissue specimens obtained from euthyroid patients undergoing parathyroidectomy. In addition, the in vivo kinetics of methimazole following single dose administration (60 mg) of carbimazole and of methimazole itself were examined in 11 healthy volunteers using high-pressure liquid chromatography to measure serum methimazole. The in vitro studies were carried out at pH 6, to avoid alkaline hydrolysis of carbimazole to methimazole. Under these conditions, methimazole strongly inhibited thyroid peroxidase. Propylthiouracil had a less pronounced inhibitory effect, and carbimazole was almost and propranolol was entirely inactive. The in vivo kinetics of methimazole showed a large interindividual variation. Within individuals, there was no significant difference in the half-life or time to peak concentration of methimazole following administration of carbimazole and methimazole, respectively. However, the peak concentration and area under the curve of methimazole were significantly greater after administration of methimazole itself than after administration of carbimazole. Assuming similar bioavailability, this difference could be related to the difference in molecular weight between carbimazole and methimazole. It appears that, in man, methimazole is the most active of antithyroid agents currently available, that carbimazole is essentially inactive per se but is bioactivated to methimazole, and that carbimazole offers neither dynamic nor kinetic advantages over methimazole.

35 citations


Journal ArticleDOI
TL;DR: The mechanism of the protective effect of induced HT on hepatic toxicity of AAP was attributed to induction of increased hepatic GSH levels resulting in decreased covalentbinding of a toxic metabolite of AAP, and enhanced glucuronidation may prevent either formation or binding of a reactive metabolite to hepatocytes, and prevention of inflammatory reaction to necrotic liver tissue.

33 citations


Journal ArticleDOI
TL;DR: To investigate the sensitization of T-lymphocytes to thyroid antigen in autoimmune thyroid disease, a modified migration inhibition factor test was employed using human peripheral T-LYmphocytes using patients with untreated Graves’ disease and Hashimoto's thyroiditis.
Abstract: To investigate the sensitization of T-lymphocytes to thyroid antigen in autoimmune thyroid disease, a modified migration inhibition factor test was employed using human peripheral T-lymphocytes. Mononuclear cells from the peripheral blood of patients with untreated Graves’ disease (GD) and Hashimoto's thyroiditis (HT) as well as from normal subjects were fractionated into E-rosetting (T-cell-enriched) and non-Erosetting (B cell- and monocyte-enriched) fractions. The migration index (MI) of T-lymphocytes from 20 patients with untreated GD and 13 patients with HT in response to either crude human thyroid antigen (88 /μg/0.5 ml) or solubilized TSH receptor antigen (20 μg/0.5 ml) was significantly inhibited compared to the unaffected migration of T-lymphocytes from 24 normal subjects. There was no correlation between these results and any of the thyroid autoantibodies. In GD patients taking propylthiouracil, the MI of T-lymphocytes in response to the thyroid antigens was inhibited in only 4 of 9 cases. The MI...

28 citations


Journal Article
TL;DR: The results suggest that the thyroid hormones may play a similar role in the growth of liver cell-derived cancers as they do in normal hepatocyte proliferation.
Abstract: 3,3′,5-Triiodo-l-thyronine (200 µg/100 g) is shown to be a potent liver parenchymal cell mitogen in the rat, and thyroidectomy is seen to severely inhibit hepatocyte proliferation in regenerating rat liver. Taken together, these observations point to a crucial role for the iodothyronine in liver cell hyperplasia. The growth rates of the transplantable Morris hepatomas 7777 and 5123tc are shown to be retarded in the surgically thyroidectomized-parathyroidectomized rat. This inhibition of tumor growth can be reversed by thyroid hormone administration. It has earlier been observed that the hypothyroid state induced in the rat by administration of propylthiouracil or radioactive iodine retarded the growth of the transplanted Morris hepatomas 7800 and 44, suggesting that these tumors were also thyroid dependent. Our results suggest that the thyroid hormones may play a similar role in the growth of liver cell-derived cancers as they do in normal hepatocyte proliferation.

26 citations


Journal ArticleDOI
TL;DR: It is suggested that propylthiouracil inhibits the GSH S-transferases in a unique fashion by competing with GSH as a substrate in reactions catalyzed by the enzymes.

24 citations


Journal ArticleDOI
TL;DR: It is suggested that post-translational steps, such as carbohydration, may play an important role in regulating the turnover of thyroglobulin and therefore influence the overall rate of thyroid hormone formation.

22 citations


Journal ArticleDOI
TL;DR: In fetal rats, the reciprocal relationship between the pituitary and the thyroid is established on approximately days 19–20 of gestation, which is based on changes in the weight and histology of the fetal thyroids.
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.

Journal Article
TL;DR: The single daily dose regimen of antithyroid drugs will control hyperthyroidism in most patients and it is found that propylthiouracil will achieve this more rapidly than methimazole.
Abstract: The effectiveness of methimazole used in a single daily dose was studied in 47 patients during their initial episode of hyperthyroidism, and in an additional eight patients during a relapse of hyperthyroidism. All patients become euthyroid using this method. Mean time required to achieve a euthyroid state was 16.7±1.1 weeks in the former group, and 14.9±2.9 weeks in the latter. In one patient there was an initial response to single daily dose therapy, but subsequently split dosage was required for control. The single daily dose regimen of antithyroid drugs will control hyperthyroidism in most patients. We have found that propylthiouracil will achieve this more rapidly than methimazole.

Journal ArticleDOI
TL;DR: In this paper, β-adrenergic receptors were identified in membranes of fetal and postnatal rat lung with (−)-[3H]dihydroalprenolol, [3H]-DHA.

Journal ArticleDOI
TL;DR: Data from a sensitive assay of [125I]TSH tropin binding to rat thyroid membranes are compatible with TSH, that is in high concentration in the serum of rats fed propylthiouracil, exerting a downregulatory influence on its own receptors.
Abstract: To investigate a possible role of TSH in the regulation of its own receptor, a sensitive assay of [I25I]TSH tropin binding to rat thyroid membranes was used. With 1 min MgCU in the buffer, Scatchard analysis of displacement of TSH gave a curvilinear plot with a high affinity, low capacity (Ki, 3.4 nM; Qi, 3.1 pmol/μg) and a low affinity, high capacity binding site (K2, 0.54 JUM; Q2, 1.2 × 0.1 nmol/μg). Feeding rats propylthiouracil led to a decrease in [125I]TSH binding (expressed either per U protein or per wet wt of tissue) that was related to the duration of treatment. Evaluation by Scatchard analysis showed that this was due to a loss of binding sites, e.g. a 50-60% decrease after 1 month of propylthiouracil treatment; affinity was actually slightly increased in the goitrous tissue. This change in the number of TSH-binding sites was readily reversed in association with the suppression of TSH in vivo either by injections of T3 for 3 days or more or by feeding a normal diet for 1 month. Thus, the data a...

Journal ArticleDOI
TL;DR: It is demonstrated that the major effect of the thyroid hormone on the metabolism of circulating mevalonate is to alter the conversion of meval onate to cholesterol, an effect localized solely to the kidneys.
Abstract: Mevalonate, an essential intermediate in cholesterol synthesis, is metabolized either to cholesterol or, by the shunt pathway, to CO2. Previous investigations have demonstrated that the kidneys are the chief site of circulating mevalonate metabolism and that sex hormones as well as insulin markedly influence circulating mevalonate metabolism. The present study examined in rats the influence of thyroid hormone status on mevalonate metabolism in vivo and in vitro. L-thyroxine administration increased renal conversion of circulating mevalonate to cholesterol, 41% in the females and 22% in the males. Conversely, hypothyroidism induced by 6 N propyl-2-thiouracil reduced renal conversion of circulatng mevalonate to cholesterol by 45% in females and 27% in males; thyroid hormone replacement in these animals returned cholesterogenesis in the kidneys to supranormal levels. Neither L-thyroxine nor hypothyroidism altered circulating mevalonate conversion to cholesterol in the liver or carcass. In vitro studies confirmed the in vivo observations. Changes in thyroid hormone produced only minor changes in the shunt pathway of mevalonate metabolism. This study demonstrates that the major effect of the thyroid hormone on the metabolism of circulating mevalonate is to alter the conversion of mevalonate to cholesterol, an effect localized solely to the kidneys.

Journal ArticleDOI
TL;DR: Data implicate both activation of the enzymes as well as increased amounts of types I and II protein kinase activity in the thyroid in response to goitrogen-induced hypertrophy and hyperplasia.

Journal ArticleDOI
TL;DR: Adult male rats were made chronically hypothyroid by surgical thyroparathyroidectomy or by feeding propylthiouracil and there was no effect on the rise in plasma TSH produced by TRH in any group, except in the group receiving t...
Abstract: Adult male rats were made chronically hypothyroid by surgical thyroparathyroidectomy or by feeding propylthiouracil. In one set of experiments, each rat was injected ip daily with doses of T4 ranging from 0.01–3.0 μg/100 g BW, which were progressively increased every 3 days. Compared to the saline-treated controls, there was no statistically significant depression of plasma TSH until doses of 0.3 μg T4/100 g BW daily had been exceeded; there was no significant rise in plasma TSH with any dose of T4. No difference was detected in the quantitative suppression of plasma TSH concentration in the thyroidectomized or propylthiouracil-treated rats, even though a given dose of T4 caused a greater rise in plasma T4 concentration in the latter. In a separate experiment, chronically thyroidectomized rats injected for 3 days with saline or with 0.01, 0.1, or 1 μg T4 for 3 days were given 100 ng TRH/100 g BW iv. There was no effect on the rise in plasma TSH produced by TRH in any group, except in the group receiving t...

Journal ArticleDOI
TL;DR: The inhibition of thyroid hormone synthesis was studied in relation to plasma levels of 6-n-propyl-2-thiouracil (PTU) through injection into adult male Sprague-Dawley rats and the accumulation of radioactivity into thyroid glands, which were removed at specified time intervals.
Abstract: The inhibition of thyroid hormone synthesis was studied in relation to plasma levels of 6-n-propyl-2-thiouracil (PTU). Na 125 I (5 μCi) was injected i.p. into adult male Sprague-Dawley rats. After 30 min, graded doses of PTU (0.2 mg/kg, 0.1 mg/kg, and 0.05 mg/kg) were similarly injected. Thyroid hormone synthesis was followed by the accumulation of radioactivity into thyroid glands, which were removed at specified time intervals. PTU levels were measured spectrophotometrically at the time of sacrifice. Additionally, PTU ( 35 S) was used to confirm blood levels of PTU and also to follow intrathyroidal PTU levels. Plasma PTU levels in excess of 0.18 μg/ml completely inhibited thyroid hormone synthesis. Levels between 0.14 and 0.09 μg/ml had a partial effect, and PTU levels less than 0.09 μg/ml had no effect on thyroid hormone synthesis.

Journal ArticleDOI
TL;DR: It is postulated that the unresponsiveness to TSH of thyroid tissue from rats fed propylthiouracil represents a down-regulation of receptor capacity, and this is effected by the binding sites becoming relatively inaccessible, rather than nonexistent.
Abstract: Using an increase in the concentration of cAMP as an index of stimulation, we previously reported that in vitro thyroid tissue of rats fed a goitrogenic diet (0.1% propylthiouracil in Purina) were unresponsive to TSH. We now show that the addition of cholera toxin (0.1-1.0 microM) to fragments of normal thyroid enhanced the concentration of cAMP. Subsequent exposure of the tissue to TSH resulted in a further increase in the concentration of cAMP, and there was statistical evidence of interaction or potentiation between the effects of TSH (20 mU/ml) and cholera toxin (1.0 microM). With fragments of thyroid from animals fed propylthiouracil (i.e. unresponsive in vitro to TSH), an increase in the concentration of cAMP was effected by 1 or 9 microM cholera toxin, and prior exposure to 9 microM toxin caused the tissue to be responsive to TSH. Unresponsiveness of the goitrous tissue was associated with a reduced capacity of the membrane to bind [125I]iodo-TSH although the affinity of the binding sites was unaffected. Cholera toxin at 0.1 microM enhanced and at 1 microM diminished the binding of [125I]iodo-TSH to membranes from either normal or goitrous glands, and these effects also reflected influences on the capacity rather than on the affinity of the binding sites. It is postulated that the unresponsiveness to TSH of thyroid tissue from rats fed propylthiouracil represents a down-regulation of receptor capacity, and this is effected by the binding sites becoming relatively inaccessible, rather than nonexistent.

Journal Article
TL;DR: Data indicate that hypothalamic control of GH secretion is unaltered in low-iodine-diet rats who maintain an euthyroid status by preferential triiodothyronine (T3) production.
Abstract: The developmental profiles of hypothalamic somatostatin and pituitary and serum growth hormone (GH) concentrations were examined in rats exposed chronically to a low iodine diet or propylthiouracil. Hypothalamic somatostatin and pituitary and serum GH concentrations were similar during development in control and low-iodine-diet animals. Propylthiouracil-induced hypothyroidism, however, was associated with reduced hypothalamic somatostatin and pituitary and serum GH concentrations, the latter being undetectable after 6 days. These data indicate that hypothalamic control of GH secretion is unaltered in low-iodine-diet rats who maintain an euthyroid status by preferential triiodothyronine (T3) production. The marked derangements observed in the hypothyroid animals indicate that thyroid hormones are critical for the postnatal maturation of the GH regulatory mechanism.

Journal ArticleDOI
TL;DR: The inhibition of the hormonogenetic processes induced by antithyroid treatment leading to a depressed iodinating activity also appears to be related to a significant impairment of the production of the Tg molecule, the specific iodine acceptor.
Abstract: The effect of 6-propyl-2-thiouracil (PTU), and 1-methyl-2-mercaptoimidazole (MMI) on thyroglobulin (Tg) biosynthesis has been studied in vivo and in vitro. In vivo experiments were performed in rats treated for 20 days with PTU or MMI, analyzing soluble and particulate, cold and 125I-labelled, Tg. Thyroglobulin biosynthesis was also investigated by in vitro experiments, incubating thyroid tissue with labelled amino acid and carbohydrate in the presence of antithyroid compounds. It has been found that in vivo antithyroid agents decrease the amount of soluble Tg and increase the proportion of particulate Tg. Tg from treated animals is poorly iodinated being mainly represented by its 12S subunit. In vitro studies demonstrate that PTU and MMI inhibit Tg biosynthesis which is impaired in the polypeptide synthesis as well as in carbohydrate chains addition. Thus the inhibition of the hormonogenetic processes induced by antithyroid treatment leading to a depressed iodinating activity also appears to be related to a significant impairment of the production of the Tg molecule, the specific iodine acceptor.

Journal ArticleDOI
01 Jan 1980
TL;DR: The results suggest that thyroid hormones promote the development of enzymes of ketone-body metabolism in the brain of hypothyroid rats after weaning in contrast to control animals.
Abstract: The changes in the developmental pattern of 3-oxo acid CoA-transferase activity in the brain of hypothyroid rats and the effect of triiodothyronine on this enzyme activity have been investigated. Hypothyroid rats showed lower activity than controls during the suckling period. However, higher enzyme levels were found in treated rats after weaning in contrast to control animals. The results suggest that thyroid hormones promote the development of enzymes of ketone-body metabolism in the brain.

Journal ArticleDOI
TL;DR: PTU+I- therapy is much more effective than PTU or I- alone in early phase treatment of hyperthyroidism, and another new finding was that the thyroid function increased again during the later addition of PTU in the patients treated with I- for one or two weeks.
Abstract: In order to compare the acute effects of three methods of treatment in hyperthyroid patients with diffuse goitre, values of thyroxine (T4), triiodothyronine (T3) in serum, T3-resin uptake (T3-U), free thyroxine index (FT4I) and free triiodothyronine index (FT3I) were employed as thyroid function parameters. In iodide (I-) group given iodine (3 or 6 mg/day) as iodinated lecithine once daily, the parameters were reduced acutely within one week after the start of treatment, reaching a plateau during the next week. In contrast to the changes in I- group, the thyroid function was decreased gradually and consistently for two weeks in the propylthiouracil (PTU 300 mg/day) group. In PT1+I- (300 mg/PTU plus 3 or 6 mg/iodide/day) group, the parameters were reduced acutely and progressively for two weeks. These results indicate that PTU+I- therapy is much more effective than PTU or I- alone in early phase treatment of hyperthyroidism. Another new finding was that the thyroid function increased again during the later addition of PTU (300 mg/day) in the patients treated with I- (3 or 6 mg/day) for one or two weeks. The well-known escape phenomenon from iodide inhibition took place counteracted the effect of PTU. Since blocking of thyroidal secretion by I- is only transient while synthesis of T3 and T4 continues, leading to greater amount of hormone stored in the gland, the treatment of hyperthyroidism with I- alone is a risky procedure.

Journal ArticleDOI
TL;DR: rT3 metabolism in patients treated for thyrotoxicosis with propylthiouracil (PTU), or methimazole (MMI) was studied by infusion of rT 3 and measurements of the increase in serum rT3 and serum 3, 3′‐diiodothyronine.
Abstract: SUMMARY rT3 metabolism in patients treated for thyrotoxicosis with propylthiouracil (PTU), or methimazole (MMI) was studied by infusion of rT3 and measurements of the increase in serum rT3 and serum 3, 3′-diiodothyronine. The results indicate that the high serum rT3 observed during treatment with PTU is not due to an increase in rT3 production, but to a decrease in the metabolic clearance rate of rT3. rT3 infusion was followed by an increase in serum 3, 3′-T2 which was similar whether PTU or MMI was given. However, after stopping rT3 infusion there was a more rapid fall in serum 3, 3′-T2 during MMI treatment, compatible with an inhibitory effect of PTU on 3, 3′-T2 degradation.

Journal ArticleDOI
TL;DR: The results are consistent with the hypothesis thatinternal iodide passes through a stage in which it is not available for organic binding before it mixes with transported iodide, and TSH appears to facilitate the transfer of internal iodide into the pool which it shares with external iodide.
Abstract: Thyroid radioiodide to serum radioiodide concentration (*T/*S) ratios 1 h after 131I administration were 3 times higher in rats pretreated with propylthiouracil (PTU) than in rats with binding thyroids. Although indications of a preponderance of transported iodide in the thyroid early after 131I injection were found, a reduction of the 1-h *T/*S ratio in TSHtreated rats by the inhibitor of iodotyrosine dehalogenation, mononitrotyrosine, points to an early contribution of intrathyroidally generated (internal) iodide to total thyroid iodide. In rat thyroids labeled 72 h earlier, there was no rise in electrophoretically separated radioiodide 2 h after the administration of PTU alone, but the elevation of thyroid iodide due to TSH was augmented by concurrently given PTU. On the assumption that PTU affects transported components of thyroid iodide identically whether they are labeled 1 or 72 h earlier, we conclude that PTU must severely depress the generation of internal iodide. This effect is no longer evident...

Journal ArticleDOI
TL;DR: White Leghorn chickens respond to dietary goitrogenic compounds by forming either colloidal or hyperplastic goiters, and it is thought that micropinocytosis is a more important endocytotic process during goiter development in the chick than is phagocytoses.
Abstract: SUMMARY White Leghorn chickens respond to dietary goitrogenic compounds by forming either colloidal or hyperplastic goiters. Thiourea does not cause increases in DNA above that seen in controls, although thyroid weight increases. This may be due to a secondary toxic effect of thiourea on the chick thyroid, which inhibits cellular replication. Both methimazole- and propylthiouracil- (PTU) fed birds exhibit cellular hyperplasia and increases in DNA amounts beyond control levels. The rapid thyroid growth in methimazoletreated birds from 30 to 70 days of age is partially due to follicular colloid accumulation. Growth of the thyroid in PTU-fed birds is thought to be due to cellular hyperplasia and hypertrophy, since DNA values are greatest in these glands. Histological studies of the thyroid glands confirm the results of DNA and protein assays for all three goitrogen-treated groups. The ultrastructural changes associated with prolonged stimulation of the chick thyroid are an increase in the amount of primary and secondary lysosomes, microvilli, and mitochondria, and a dilation of the endoplasmic reticulum and Golgi apparatus. It is thought that micropinocytosis is a more important endocytotic process during goiter development in the chick than is phagocytosis.

Journal ArticleDOI
TL;DR: Alteration of thyroid status, and specifically T4 level is indicated to be a contributing factor in the regulation of serum HEX activity in humans, as evidenced by individual responsiveness to oral administration of this hormone, or inhibitors of its peripheral metabolism.

Journal ArticleDOI
TL;DR: It is demonstrated that CPIB has both glycogenolytic and hypolipidemic effects and its action does not seem to be mediated by thyroid hormones and possibly involves changes in pancreatic glucagon and insulin secretion.

Journal ArticleDOI
TL;DR: Analyses of subfractions of the enzyme indicated that only IB-type enzyme changed in response to thyroid hormone action, also irrespective of the presence or absence of the pituitary.
Abstract: After having defined reliable assay conditions for free and template-bound RNA polymerase I activities, we examined in detail the effect of thyroid hormone in vivo on nucleolar RNA polymerase I in rat liver. The enzyme activity decreased markedly in the hypothyroid state produced by either thyroidectomy, hypophysectomy or by administration of propylthiouracil (PTU). One large dose (25 microgram/100 g body weight) of T3 given intraperitoneally caused a rapid recovery of the enzyme activity within 24 h either in the presence or absence of the pituitary. The enzyme activity of both free and chromatin-bound enzyme changed in parallel throughout. A similar recovery was noted after daily subcutaneous injections of a physiological dose (1 microgram/100 g body weight) of T3 for about 3 weeks. Analyses of subfractions of the enzyme indicated that only IB-type enzyme (the enzyme fraction containing the whole set of subunits) changed in response to thyroid hormone action, also irrespective of the presence or absence of the pituitary. The possibility that thyroid hormone is a major physiological regulator of the synthesis of RNA polymerase I in rat liver is discussed.