Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.11.1.7 (peroxidase)
 65,474 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thyroid hormone formation requires the coincident presence of peroxidase, H2O2, iodide, and acceptor protein at one anatomic locus in the cell. The peroxidase enzyme appears to be a protoporphyrin lX containing heme protein, with binding sites for both iodide and tyrosine. It is probable that both iodide and tyrosine are oxidized to free radical forms which unite to form iodotyrosine. The peroxidase is also involved through an uncertain mechanism in iodotyrosine coupling and probably in oxidation of sulfhydryl bonds in thyroglobulin. H2O2 may be supplied by microsomal NADPH-cytochrome c reductase or NADH-cytochrome b5 reductase. Other possible intracellular H2OI generating systems include monoamine oxidase and xanthine oxidase. The usual acceptor for iodide is thyroglobulin, which is currently believed to be iodinated within apical secretory vesicles at the cell border just prior to liberation into the colloid, or possibly after liberation into the colloid. Other soluble an insoluble proteins are also iodinated within the gland. The peroxidase is present in numerous cellular structures, but iodination activity occurs primarily, if not only, at the apical cell border. The controls of iodination are imperfectly known. Thyrotrophin modulation of iodide uptake, H2O2 generation, thyroglobulin synthesis, and peroxidase enzyme level obviously are the main regulations. Many of these actions are thought to involve mediation of adenyl cyclase and subsequent activation of intracellular phosphokinases. Antithyroid drugs of the thiocarbamide group are competitive inhibitors of iodination under some circumstances, but if much iodide is present, they react with the oxidized iodine intermediate and are irreversibly inactivated themselves. Clinical problems involving defective peroxidase function are among the most frequent hereditary defects of thyroid hormone formation. Recognized abnormalities include deficient peroxidase, abnormality in binding of the peroxidase apoprotein to its prosthetic group, and other less well-identified abnormalities in peroxidase structure and function. Peroxidase is typically elevated in thyroid tissue from patients with hyperthyroidism sometimes deficient in cold thyroid nodules, and frequently diminished in tissue from patients with Hashimoto's thyroiditis.
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PMID:Biosynthesis of thyroid hormone: basic and clinical aspects. 6 47

There is evidence to suggest that elevated levels of iodide in the diet are associated with autoimmune thyroid disease (ATD) in susceptible individuals, and that autoimmune thyroiditis (Hashimoto's disease) is less common in susceptible individuals who live in regions with dietary iodine deficiency. There are epidemiologic studies in endemic goiter areas that report an increase in ATD, particularly thyroiditis, after the therapeutic administration of iodized salt, bread and oil. Lymphocytic infiltration of the thyroid is rarely found in patients from severe endemic goiter regions, yet there is a reversal of this observation after dietary iodine supplementation. Thyroid antibodies, both thyroglobulin (TgAb) and peroxidase (TpAb) or microsomal, were not detected in serum from patients with endemic goiter, but became positive in 43% of subjects three and six months after therapy with iodized oil, and there developed transient hyperthyroidism. Similarly, the addition of iodine to the diet or the administration of iodine-containing medications increases the frequency of ATD and the severity of existing autoimmune thyroiditis. Furthermore, autoimmune thyroiditis has been induced by the administration of excess iodide to strains of chickens and rats that are genetically predetermined to develop the disease. We are beginning to understand the pathogenesis of ATD. In hyperthyroidism the evidence clearly supports the hypothesis that TSH receptor antibodies (TRAb) stimulate the TSH receptor to induce excessive and sustained secretion of thyroid hormones. Cellmediated immune mechanisms, such as antibody dependent cellmediated cytotoxicity (ADCC), initiate the lymphocytic infiltration and thyrocytotoxicity in autoimmune thyroiditis. The mechanisms that initiate the development of the abnormal immune response and the relationship of ATD with excess iodide are poorly understood. There is evidence that an increase in the iodination of thyroglobulin (Tg) enhances its immunogenicity. The results of clinical and experimental studies support the requirement of a genetic predisposition to the development of ATD that may be precipitated by exposure to certain environmental factors. Another mechanism supported by experimental data is the direct toxic effect of excess iodide on iodide-deficient thyroid glands. High concentrations of iodide after oxidation to iodine causes epithelial necrosis and inflammation associated with lipofuscin accumulation suggestive of toxicity mediated by lipid peroxidation from excessive amounts of free radicals. The epithelial damage would initiate inflammatory and immune responses. Although these mechanisms would relate to the onset of autoimmune thyroiditis on exposure to excessive amounts of iodide, the relationship of iodide intake and autoimmune hyperthyroidism is less clear.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The relationship between autoimmune thyroid disease and iodine intake: a review. 134 85

Evidence has accumulated in the last few years that the expression of the microsomal/peroxidase antigen (M/TPO-Ag) in thyroid cells is induced by TSH, through pathways which involve intracellular cAMP accumulation and protein synthesis. These data have been found true in any thyroid system studied so far, both in terms of immunologic and enzymatic activity of TPO. TSH and cAMP also increase the levels of the specific mRNA for TPO in thyroid cells from different species. Whether this phenomenon is due to a direct transcriptional regulation of the TPO gene, as shown in dog thyroid cells, or to posttranscriptional effects, as it would appear in FRTL-5 cells, remains to be clarified by future experiments. Thyroid stimulating antibody (TSAb) of Graves' disease also stimulates the expression of M/TPO-Ag. This finding gives further support to the relevance of TSAb in the pathogenesis of hyperthyroidism and explains the well known observation that the "microsomal" antigen is particularly abundant in glands of Graves' patients. The modulation of M/TPO-Ag surface expression by TSH can explain the decrease of circulating anti-MAb observed during L-thyroxine therapy in hypothyroid patients with Hashimoto's thyroiditis. Other agents, such as methimazole and sodium iodide, which influence thyroid cell function, do not directly interfere with the expression of M/TPO-Ag. Cytokines, such as gamma-interferon, interleukin-1, and interleukin-6 have been shown to inhibit the TSH-induced increase of TPO mRNA, but further investigations are required to elucidate the exact role of cytokines in the regulation of M/TPO-Ag expression.
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PMID:The microsomal/peroxidase antigen: modulation of its expression in thyroid cells. 166 95

This paper describes the use of an ELISA technique to assess the involvement of the complement system in the pathogenesis of autoimmune thyroid disease (AITD). Microtitre plates coated with thyroid membrane antigen were exposed to serum samples obtained from AITD patients, all of whom showed elevated levels of circulating anti-thyroid autoantibodies, and dilute guinea pig serum, as a source of complement, was then added to the microtitre wells. The degree of activation of the classical complement pathway was assessed by measuring the bound complement component C3 using a peroxidase conjugated anti-guinea pig C3 antiserum. C3 fixation and activation was greater in the presence of serum from patients with Hashimoto's disease when compared with that seen in patients with autoimmune hyperthyroidism (Graves' disease). Serum samples obtained from normal healthy volunteers and from patients with thyroid neoplasia were negative in this assay. The method allows the calculation of a putative "biologically active autoantibody" level and analysis of these data confirm our earlier observation that the species of autoantibody found in autoimmune hypothyroidism are potentially more destructive than those found in other forms of AITD.
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PMID:Elisa for the measurement of complement C3 activation by autoantibodies directed against thyroid membrane antigens. 166 67

A rare case of simultaneous hypersecretion of thyroid stimulating hormone (TSH) and growth hormone (GH) in a pituitary adenoma is reported. A 59-year-old male complaining of general fatigue, dyspnea on exertion and finger tremor was admitted. Examination on admission, he revealed with hyperthyroidism and hypersecretion of TSH and thyroid hormones. Administration of TRH did not further increase serum TSH level, and administration of T3 also had no effect on TSH secretion. CT scan showed a pituitary macroadenoma 13mm in diameter. MRI demonstrated a homogenously hypointense mass with Gd-DTPA enhancement in the left side of the sella turcica. The entire chromophobic adenoma was removed by trans-sphenoidal surgery. Immunostaining of the specimen showed that the cytoplasm of the adenoma cells was positive for both TSH and GH. Double immunostaining using avidin-biotin-peroxidase complex (ABC) method and immunogold silver staining (IGSS) method, showed that the adenoma cells had been secreting both GH and TSH at the same time. After the adenomectomy, the hyperthyroidism disappeared, and all altered indicators of pituitary function returned to normal.
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PMID:[A case of pituitary adenoma with simultaneous secretion of TSH and GH detected by double immunostaining method]. 193 Dec 60

To evaluate possible immunological mechanisms involved in the development of postpartum thyroiditis with transient hyperthyroidism followed by transient hypothyroidism (PPT), antithyroid peroxidase antibodies (anti-TPO), antimicrosomal antibody (AMA) related immunoglobin G subclass and antibody-dependent cell-mediated cytotoxicity (ADCC) were studied in 43 post-partum (PP) women who were euthyroid at delivery and completed a subsequent 1 year follow up. Among the 25 mothers who developed PPT, 14 had positive AMA (PPT:AMA+) and 11 negative AMA (PPT:AMA-) at delivery. Among the 18 mothers who remained euthyroid (E) up to one year post-partum and were used as controls, 8 were AMA positive (E:AMA+) and 10 AMA negative (E:AMA-) at delivery. AMA measured by a hemagglutination method correlated well with anti-TPO antibodies measured by RIA in the PP mothers studied. When AMA-related IgG subclass activity was analysed comparing PPT women with appropriate euthyroid controls at the different time intervals studied, it was seen that PPT:AMA+ when compared to E:AMA+ women have significantly increased activity of AMA related IgG1 at all PP time intervals studied (p less than 0.001), but IgG4 was only increased at 5-7 months PP (p less than 0.05). PPT:AMA-when compared to E:AMA- have significantly increased IgG4 at 2-4 (p less than 0.001), 5-7 and 10-12 (p less than 0.05) months PP, but IgG1 is only increased at 5-7 months PP (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increase in antimicrosomal antibody-related IgG1 and IgG4, and titers of antithyroid peroxidase antibodies, but not antibody dependent cell-mediated cytotoxicity in post-partum thyroiditis with transient hyperthyroidism. 209 Jun 68

In the rat, functional connections between the splanchnic nerve and the adrenal medulla are immature at birth and do not become fully competent until the first postnatal week. Neonatal administration of triiodothyronine (T3) accelerates this process, and the present study was undertaken to elucidate the underlying mechanisms. Rats were given T3 (0.1 mg/kg, s.c.) daily for 9 days beginning 1 day after birth. Preganglionic innervation of the adrenal medulla was examined by retrograde axonal transport of horseradish peroxidase (HRP). At 10 days of age, there was an increased number of labeled perikarya in the spinal cord of the hyperthyroid pups. Ultrastructural examination revealed a corresponding increase in synaptic density in the adrenal medulla and in the activity of choline acetyltransferase, a marker for preganglionic cholinergic nerve terminals. These effects were attenuated by 25 days of age, whereupon deficits in HRP-labeled neurons and adrenomedullary synapses were noted. Similarly, replication of chromaffin cells was enhanced transiently in the T3 group during the initial stage of hyperthyroidism, but subsequent long-lasting deficits in cell numbers were noted, along with a corresponding retardation of ontogeny of adrenal catecholamine biosynthesis and storage. Thus, neonatal hyperthyroidism accelerates synaptic development in the sympatho-adrenal axis but suppresses maturation of the target chromaffin cells, ultimately leading to impaired adrenomedullary function.
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PMID:Thyroid hormone control of preganglionic innervation of the adrenal medulla and chromaffin cell development in the rat. An ultrastructural, morphometric and biochemical evaluation. 246 85

Intracellular localization of and an assay method for endogenous peroxidase (PO) activity were studied using primary culture of thyroid cells obtained from patients with hyperthyroidism. PO activity was visualized by cytochemical reaction and was located mainly in perinuclear cisternae and rough endoplasmic reticulum. With increased culture time, the number of cells showing positive PO activity and amount of the enzyme reaction product in individual cells showed a parallel decrease. For measurement of PO activity, cultured thyroid cells were frozen and thawed and then incubated with citric acid buffer solution containing o-phenylenediamine (opd) and hydrogen peroxide. After incubation, the optical density (OD) of the solution colorized by endogenous peroxidase was measured at 405 nm using a microplate reader. About 1 X 10(4) cells were sufficient for assay of PO activity. Using the above method to assay PO activity and sandwich enzyme immunoassay for thyroglobulin (TG), chronological changes in the PO activity and TG concentration in the culture medium were examined. Although the cells showed no decrease in number, PO activity and TG concentration decreased chronologically. When the ratio of PO activity to TG concentration was calculated, in 3 cases the ratio was almost constant, and in the remaining two, it decreased chronologically. The present biochemical method thus seems useful for determining peroxidase activity of cultured thyroid en masse.
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PMID:Endogenous peroxidase activity in primary culture of human thyroid cells. Localization and measurement. 340 Apr 65

Twenty-six patients with Graves' hyperthyroidism treated only with propranolol for 1-21 months have been followed up to 5 years. The patients were evaluated before treatment, at 15, 30, and 90 days during treatment, and then at 90-day intervals during propranolol treatment by clinical examination and measurement of serum free T3, free T4, rT3, TSH, and sex hormone-binding globulin concentrations and serum anti-thyroglobulin, antithyroid microsomal, antithyroid peroxidase, and thyroid-stimulating autoantibodies. Eighteen patients who had no biochemical improvement during propranolol therapy or relapsed after initial improvement were treated conventionally. In contrast, eight patients had a biochemical remission, which has lasted 30-48 months after propranolol withdrawal. The biochemical values before and during treatment did not differ among the two groups of patients, except for the initial serum free T3 levels which were significantly higher in the patients who had no remission. Serum TSH levels returned to normal only in patients who had a long-lasting remission. While thyroid autoantibodies decreased or disappeared during follow-up, the evolution of thyroid-stimulating autoantibody values was grossly related to the clinical outcome. Long-lasting remissions may occur in patients with hyperthyroidism due to Graves' disease not given ablative or antithyroid drug therapy. Since propranolol is devoid of antithyroid and immunosuppressive actions, these remissions are probably spontaneous. Although they tended to occur in patients with less severe disease, no biological parameter was found that predicted the outcome.
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PMID:Lasting remissions in patients treated for Graves' hyperthyroidism with propranolol alone: a pattern of spontaneous evolution of the disease. 341 46

Using lectin-peroxidase technique, the influence of hypo- and hyperthyroidism on histotopography of glycoconjugates has been investigated in rat submandibular gland. The following lectins were used: peanut agglutinin (PNA), wheat germ agglutinin (WGA), Laburnum anagyroides lectin (LAL) and concanavalin A (con A). It has been demonstrated that hyperthyroidism is accompanied by the loss of con A, WGA and LAL receptor sites. Hypothyrodism enhanced con A binding to granular duct cells with a parallel reduction in WGA and LAL binding to these or other duct cells. Hypothyroidism as well as hyperthyroidism markedly enhanced PNA binding to duct epitheliocytes with redistribution of these lectin binding sites from the luminal surface of salivary ducts into the cytoplasm of duct cells. Possible interpretations of the observed phenomena are discussed.
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PMID:[Effect of thyroid hormones on the histotopography of lectin receptors in the rat salivary gland]. 356 50


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