Presence of a soluble inhibitor of thyroid iodination in primary cultures of thyroid cells.
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Monolayer cultures of thyroid cells lose their iodide organification capacity a few days before the disappearance of thyroid peroxidase (TPO) activity. The present studies were performed in order to clarify this point. The above mentioned difference was due to the presence of an inhibitor in the monolayer thyroid cells culture, given that total homogenate prepared from confluent cells caused a significant inhibition of activity of TPO from fresh tissue. The inhibitor was localized in the 105000g supernatant of the homogenate of the cell culture, but not in a similar preparation obtained from fresh thyroid. It is thermostable, dialyzable and has a molecular weight of less than 2 kDa. Addition of the inhibitor at the end of the reaction of tyrosine iodination failed to alter the results. This fact suggests that the compound does not destroy the iodinated product. The presence of the cytosolic inhibitor was observed in monolayer thyroid cell cultures of different species (bovine, porcine, rat and human) but not in free follicles cultures. (+info)
Differential expression of mRNA in human thyroid cells depleted of mitochondrial DNA by ethidium bromide treatment.
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A wide variety of human diseases have been associated with defects in mitochondrial DNA (mtDNA). The exact mechanism by which specific mtDNA mutations cause disease is unknown and, although the disparate phenotypes might be explained on the basis of impaired mitochondrial gene function alone, the role of altered nuclear gene expression must also be considered. In recent years, the experimental technique of depleting cells of mtDNA by culturing them with ethidium bromide has become a popular method of studying mitochondrial disorders. However, apart from depleting mtDNA, ethidium bromide may have many other intracellular and nuclear effects. The aim of the present study was to investigate the effects of ethidium bromide treatment on nuclear gene expression. A simian-virus-40-transformed human thyroid cell line was depleted of mtDNA by culture in ethidium bromide, and differential display reverse transcriptase-PCR (DDRT-PCR) was then employed to compare mRNA expression between wild-type, mtDNA-replete (rho(+)) and ethidium bromide-treated, mtDNA-depleted (rho(0)) cells. Expression of the majority of nuclear-encoded genes, including those for subunits involved in oxidative phosphorylation, remained unaffected by the treatment. Seven clones were found to be underexpressed; three of the clones showed significant similarity with sequences of the human genes encoding RNase L inhibitor, human tissue factor and ARCN1 (archain vesicle transport protein 1), a highly conserved species which is related to vesicle structure and trafficking proteins. We conclude that the effects of ethidium bromide treatment on nuclear gene expression are not simply limited to changes in pathways directly associated with known mitochondrial function. Further studies will be required to elucidate which of these changes are due to mtDNA depletion, ATP deficiency or other disparate effects of ethidium bromide exposure. Given that most genes appear unaffected, the results suggest that depleting cells of mtDNA by ethidium bromide treatment is a valuable approach for the study of mitochondrial mutations by cybrid techniques. (+info)
Sensitivity of thyroid gland growth to thyroid stimulating hormone (TSH) in rats treated with antithyroid drugs.
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Antithyroid drugs and phenobarbital (PB) have been shown to promote thyroid tumors in rats. It has been proposed that increased thyroid-stimulating hormone (TSH) mediates the thyroid tumor-promoting effect of antithyroid drugs and PB, and is increased because of decreased thyroxine (T4) concentration. However, PB is much less effective than antithyroid drugs at increasing TSH. It has been proposed that small increases in serum TSH produced by PB treatment is sufficient to promote thyroid tumors. However, the level to which TSH must be increased to stimulate the thyroid gland has not been reported. Therefore, we have examined the effect of increasing serum TSH concentration on thyroid growth by measuring thyroid gland weight and thyroid follicular cell proliferation. Serum TSH concentrations were increased by feeding rats various concentrations of propylthiouracil (PTU) or methimazole (MMI) for 21 days. Serum total T4, free T4, total T3 (triiodothyronine), free T3, and TSH concentrations were measured by radioimmunoassay. Thyroid follicular cell proliferation was measured by autoradiography and expressed as a labeling index (LI). PTU and MMI treatments reduced total and free T4 more than 95% by day 21, whereas total and free T3 were reduced 60%. TSH, thyroid follicular cell proliferation and thyroid weight were increased 560%, 1400%, and 200%, respectively, by day 21. TSH was significantly correlated with thyroid weight and LI. Moderate increases in serum TSH of between 10 and 20 ng/ml increased the number of proliferating thyroid follicular cells, but had no effect on thyroid weight. These results support that small increases in serum TSH can be sufficient to stimulate thyroid follicular cell proliferation. Furthermore, thyroid follicular cell proliferation may be more useful than thyroid weight alone for assessing alterations in thyroid growth in rats treated with chemicals that produce only small to moderate increases in serum TSH. (+info)
Characterization of potential endocrine-related health effects at low-dose levels of exposure to PCBs.
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This article addresses issues related to the characterization of endocrine-related health effects resulting from low-level exposures to polychlorinated biphenyls (PCBs). It is not intended to be a comprehensive review of the literature but reflects workshop discussions. "The Characterizing the Effects of Endocrine Disruptors on Human Health at Environmental Exposure Levels," workshop provided a forum to discuss the methods and data needed to improve risk assessments of endocrine disruptors. This article contains an overview of endocrine-related (estrogen and thyroid system) interactions and other low-dose effects of PCBs. The data set on endocrine effects includes results obtained from mechanistic methods/ and models (receptor based, metabolism based, and transport protein based), as well as from (italic)in vivo(/italic) models, including studies with experimental animals and wildlife species. Other low-dose effects induced by PCBs, such as neurodevelopmental and reproductive effects and endocrine-sensitive tumors, have been evaluated with respect to a possible causative linkage with PCB-induced alterations in endocrine systems. In addition, studies of low-dose exposure and effects in human populations are presented and critically evaluated. A list of conclusions and recommendations is included. (+info)
A case of Graves' disease associated with autoimmune hepatitis and mixed connective tissue disease.
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The patient was a woman of forty-eight. Liver dysfunction was pointed out at the age of forty-five. She was admitted to hospital because of her hyperthyroidism. Her palmar skin was wet and her fingers were swollen like sausages. She had a diffuse and elastic hard goiter with a rough surface. The serum levels of free T3 (9.6 pg/mL) and free T4 (3.76 ng/dL) were high and that of TSH (0.11 microU/mL) was low. The activity of TSH-binding inhibitory immunoglobulin (TBII) was 89%. The uptake rate of 123I to the thyroid was 55.1% and the uptake pattern was nearly diffuse. The goiter was proved to contain several nodules by ultrasonography, but aspiration cytology showed no malignant cells. She was diagnosed to have Graves' disease with adenomatous goiter. She also had high ALT (34 IU/L) and gamma-globulin (1.97 g/dL). She had positive antinuclear antibody (speckled type), positive anti-ribosomal nuclear protein antibody, and positive LE cell phenomenon. The liver biopsy revealed mononuclear cell infiltration with fibrosis in the portal area. These data indicated that she also had autoimmune hepatitis (AIH) and mixed connective tissue disease (MCTD). The analysis of human leukocyte antigen (HLA) showed positive A11 which had been reported to relate to Graves' disease, and positive DR4 which had been reported to relate to AIH and MCTD. These results suggested that HLA would determine susceptibility to three distinct autoimmune diseases in this case. (+info)
A case of amyloid goiter secondary to Crohn's disease.
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We herewith report a case of amyloid goiter secondary to Crohn's disease. The patient had been diagnosed as having Crohn's disease at the age of 15, and underwent right hemicolectomy at age 20. When he was 26 years old he complained of swelling of the anterior neck. Both TSH and thyroid hormones were within the normal range, and anti-thyroglobulin and anti-microsomal antibodies were negative. Only thyroglobulin was noticeably above the normal range. During the next year his goiter enlarged further and because he had a feeling of pressure he underwent total thyroidectomy. The presence of amyloid A protein in his surgical specimen led to the diagnosis of amyloid goiter. Although most cases of secondary amyloidosis are known to develop in neoplasms or chronic inflammatory diseases, our patient had no illness other than Crohn's disease. Perusal of literature revealed that Crohn's disease is rarely a cause of amyloid goiter. (+info)
Suppressive therapy with levothyroxine for euthyroid diffuse and nodular goiter.
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In this study, 35 patients with euthyroid diffuse goiter and 35 patients with euthyroid nodular goiter were treated with Levothyroxine (L-T4) for six months. The aim was to evaluate the efficacy of treatment on thyroid and nodule volumes and to evaluate the correlation between volume changes and thyroglobulin levels. Serum thyroid hormones, TSH, thyroglobulin, thyroid and nodule volumes were measured at the initial visit and after 6 months. Radioactive iodine uptakes of the thyroid gland were evaluated before treatment. The mean decrease of thyroid volume at six months was about 20% (20.4 +/- 8.8 ml vs. 16 +/- 7.9 ml, P<0.001) in patients with diffuse goiter. All patients with diffuse goiter showed some decrement in their goiter sizes. Thyroid nodules, in response to thyroid hormone treatment, showed a variable behavior. A reduction of 50% or more in volume was detected in 31% (11/35) of the patients. 54% of the patients (19/35) showed a 10-49% decrease in nodule volume. Five of the patients were found to be insensitive to the therapy. Their nodule volumes either increased or did not change during therapy. Free T4 and free T3 levels increased and TSH levels decreased with L-T4 treatment in all patient groups. Patients with higher TSH levels (within normal limits) showed more volume reduction in the diffuse goiter group. No uniform correlation was found between volume changes and thyroglobulin levels in either of the patient groups. In conclusion, suppressive thyroxine treatment is effective in reducing the size of the goiter, and nodules and thyroglobulin levels cannot be taken as an indicator of the efficacy of L-T4 therapy. (+info)
Changes in thyroid function during development of thyroid hyperplasia induced by kojic acid in F344 rats.
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To clarify the mechanism of tumorigenesis by kojic acid (KA), dose and time dependence of iodine uptake in the thyroid gland and serum thyroid stimulating hormone (TSH) and thyroid hormone levels were investigated in F344 rats fed a diet containing 2% KA. After 4 weeks, thyroid hyperplasia was apparent in males, associated with a decrease in (125)I uptake into the thyroid gland to only 3% of that in controls. The serum triiodothyronine (T(3)) and thyroxine (T(4)) levels dropped to 0.36 ng/ml, 1.7 micrograms/dl from the initial values of 0.61 ng/ml, 4.0 micrograms/dl and TSH increased seven times to 15 ng/ml. In females, the effects on thyroid weight and (125)I uptake were less prominent, although the changes in serum T(3), T(4) and TSH levels were similar to those in males. Time-dependent changes in serum T(3), T(4) and TSH levels correlated with the inhibition of iodine uptake in the thyroid. Inhibition of organic iodine formation was only observed after 3 weeks treatment. On return to the control diet, normal serum T(3), T(4) and TSH levels became evident within 48 h in both sexes. These data suggest that KA interrupts thyroid function, primarily by inhibiting iodine intake, consequently causing a decrease in serum T(3) and T(4). Increased TSH from the pituitary gland in turn stimulates thyroid hyperplasia, which is reversible on withdrawal of KA. (+info)