Iodide Organification Defect in a Cold Thyroid Nodule: Absence of Iodide Effect on Cyclic Amp Accumulation

Demeester-Mirkine, N; Sande, Jacqueline Van; Dor, Pierre; Heimann, R; Cochaux, Pascale; Dumont, Jacques Emile

doi:10.1111/j.1365-2265.1984.tb03444.x

Cited by 9 publications

(6 citation statements)

References 24 publications

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“…The following facts suggest that this also applies to intact follicles. 1) Exogenous supply of H 2 O 2 greatly enhances iodination in thyroid slices (3,24). 2) TSH, which enhances iodination in dog thyroid, also activates H 2 O 2 generation in this system (5).…”

Section: Discussionmentioning

confidence: 98%

The H2O2-Generating System Modulates Protein Iodination and the Activity of the Pentose Phosphate Pathway in Dog Thyroid*

Corvilain¹,

Sande²,

Laurent³

et al. 1991

Endocrinology

155

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Iodide oxidation and binding to proteins require a thyroperoxidase and an ill defined H2O2-generating system. The NADP+ supply and, thus, NADPH oxidation are the limiting steps of the pentose phosphate pathway. The purpose of this work was to test the hypothesis that H2O2 generation is a limiting step of iodination and NADPH oxidation and, therefore, of the pentose phosphate pathway. H2O2 produced by dog thyroid slices was measured with the homovanillic fluorescence assay. Our data show that H2O2 generation is stimulated by both the cAMP cascade [as activated by TSH, forskolin and (Bu)2cAMP] and the Ca2(+)-phosphatidylinositol cascade (as activated by carbamylcholine, ionomycin, and 12-O-tetradecanoylphorbol-13-acetate). We used several physiological and pharmacological agents that modulate iodide organification. In all cases there was a strict parallelism between effects on H2O2 generation, iodide binding to proteins, and pentose phosphate pathway activity. Moreover, in TSH- or carbamylcholine-stimulated slices, glucose or Ca2+ depletion, which greatly depressed H2O2 generation, also greatly decreased iodide organification and the activity of the pentose phosphate pathway. The glutathione peroxidase-catalyzed H2O2 reduction in the cytosol, which involves NADPH oxidation and, therefore, increases the NADP supply, also enhances the activity of the pentose phosphate pathway. All of these data strongly support the hypothesis that H2O2 generation in dog thyroid controls iodination of proteins; through the NADPH oxidation resulting from H2O2 production and reduction, hydrogen peroxide also regulates the activity of the pentose phosphate pathway.

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Section: Discussionmentioning

confidence: 98%

The H2O2-Generating System Modulates Protein Iodination and the Activity of the Pentose Phosphate Pathway in Dog Thyroid*

Corvilain¹,

Sande²,

Laurent³

et al. 1991

Endocrinology

155

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“…It should allow to demonstrate the genetic lesion of this system in iodination defects observed in congenital hypothyroidism, thyroid cold adenomas, and thyroid cancer with normal thyroperoxidase (43,44). The close proximity of thyroperoxidase and ThOX at the apical pole of thyrocytes suggests that autoimmune reactions leading to the generation of autoantibodies directed against the former might spread to the latter in Hashimoto's thyroiditis or Graves' diseases.…”

Section: Discussionmentioning

confidence: 99%

Cloning of Two Human Thyroid cDNAs Encoding New Members of the NADPH Oxidase Family

Deken¹,

Wang²,

Many³

et al. 2000

Journal of Biological Chemistry

560

460

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Two cDNAs encoding NADPH oxidases and constituting the thyroid H 2 O 2 generating system have been cloned. The strategy of cloning was based on the functional similarities between H 2 O 2 generation in leukocytes and the thyroid, according to the hypothesis that one of the components of the thyroid system would belong to the gp91 Phox /Mox1 gene family and display sequence similarities with gp91Phox . Screening at low stringency with a gp91Phox probe of cDNA libraries from thyroid cells in primary culture yielded two distinct human cDNA clones harboring open reading frames of 1551 (ThOX1) and 1548 amino acids (ThOX2), respectively. The encoded polypeptides display 83% sequence similarity and are clearly related to gp91Phox (53 and 47% similarity). The theoretical molecular mass of 177 kDa is close to the apparent molecular mass of 180 kDa of the native corresponding porcine flavoprotein and the protein(s) detected by Western blot in dog and human thyroid. ThOX1 and ThOX2 display sequence similarities of 53% and 61%, respectively, with a predicted protein of Caenorhabditis elegans over their entire length. They show along their first 500 amino acids a similarity of 43% with thyroperoxidase. The corresponding genes of ThOX1 and ThOX2 are closely linked on chromosome 15q15.3. The dog mRNA expression is thyroid-specific and up-regulated by agents activating the cAMP pathway as is the synthesis of the polypeptides they are coding for. In human thyroid the positive regulation by cAMP is less pronounced. The proteins ThOX1 and ThOX2 accumulate at the apical membrane of thyrocytes and are co-localized with thyroperoxidase.

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“…In vitro studies performed in two cases (6,21) suggested that the defect does not reside in thyroid peroxidase but in the H 2 O 2 generating system.…”

Section: Discussionmentioning

confidence: 96%

“…Because all the follicular carcinomas showed the trapping-only phenomenon, the authors suggested that this pattern might be associated with follicular cancer. However, these data were not generally confirmed in subsequent studies where the majority of patients had benign nodules (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26). Therefore, the actual prevalence of the trapping-only phenomenon and its possible association with thyroid malignancy is still an open question.…”

Section: Introductionmentioning

confidence: 86%

The Trapping-Only Nodules of the Thyroid Gland: Prevalence Study

Reschini

Ferrari²,

Castellani

et al. 2006

Thyroid

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The aim of this study was to determine the prevalence of trapping-only nodules of the thyroid gland. The study was prospectively performed in patients bearing hot or warm thyroid nodules at pertechnetate scan in the presence of circulating thyrotropin (TSH) within the normal range. The study was restricted to these patients because nodules that suppress TSH are certainly autonomous. In 140 patients showing hot or warm nodules at 30-minute pertechnetate scintigraphy, and normal TSH levels, radioiodine scintigraphy was performed at 24 hours. The trapping-only pattern, i.e., the presence of a cold nodule in late radioiodine scintigraphy was observed in seven patients (5%). Five had benign thyroid nodules, one follicular carcinoma, and one extrathyroid metastases of papillary-follicular carcinoma. Despite controversy on this issue, trapping-only nodules of thyroid should be searched because they have risk of malignancy and must be differentiated from autonomous adenomas at the compensated stage. The search may be limited to patients with normal serum TSH.

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Iodide Organification Defect in a Cold Thyroid Nodule: Absence of Iodide Effect on Cyclic Amp Accumulation

Cited by 9 publications

References 24 publications

The H2O2-Generating System Modulates Protein Iodination and the Activity of the Pentose Phosphate Pathway in Dog Thyroid*

The H2O2-Generating System Modulates Protein Iodination and the Activity of the Pentose Phosphate Pathway in Dog Thyroid*

Cloning of Two Human Thyroid cDNAs Encoding New Members of the NADPH Oxidase Family

The Trapping-Only Nodules of the Thyroid Gland: Prevalence Study

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