scholarly journals Increased Expression of the Na+/I− Symporter in Cultured Human Thyroid Cells Exposed to Thyrotropin and in Graves’ Thyroid Tissue*

1997 ◽  
Vol 82 (10) ◽  
pp. 3331-3336 ◽  
Author(s):  
Tsukasa Saito ◽  
Toyoshi Endo ◽  
Akio Kawaguchi ◽  
Masato Ikeda ◽  
Minoru Nakazato ◽  
...  
Keyword(s):  
Thyroid Tissue ◽  
Human Thyroid ◽  
Thyroid Peroxidase ◽  
Graves Disease ◽  
Intracellular Camp ◽  
Normal Thyroid Tissue ◽  
Thyroid Cells ◽  
Normal Thyroid ◽  
Hormone Synthesis ◽  
Messenger Ribonucleic Acid

Abstract The Na+/I− symporter (NIS) is important in hormone synthesis in the thyroid gland. NIS activity, as reflected by I− uptake, was increased by TSH (1 mU/mL) or forskolin (10μ mol/L) in primary cultured human thyroid cells. Northern blot analysis revealed that incubation of these cells with TSH or forskolin for 24 h increased the abundance of NIS messenger ribonucleic acid (mRNA) 2.3- and 2.5-fold, respectively. Immunoblot analysis revealed 2.7- and 2.4-fold increases, respectively, in the amount of NIS protein after 48 h, suggesting that elevated levels of intracellular cAMP induced the expression of NIS in human thyrocytes. We then studied the levels of NIS mRNA and protein in Graves’ thyroid tissue and found that the amount of NIS mRNA in thyroid tissue from individuals with Graves’ disease (n = 5) was 3.8 times that in normal thyroid tissue (n = 5). The abundance of NIS mRNA was significantly correlated with that of thyroid peroxidase or thyroglobulin mRNAs, but not with that of TSH receptor mRNA, in the Graves’ and normal thyroid tissue specimens. The amount of NIS protein was also increased 3.1-fold in Graves’ thyroid tissue compared with that in normal thyroid tissue. The increased expression of NIS may thus contribute to the development of Graves’ disease.

Isolation of a cDNA whose expression is markedly increased in malignantly transformed FRTL cells and neoplastic human thyroid tissues

1994 ◽  
Vol 12 (1) ◽  
pp. 85-92
Author(s):  
K Ohta ◽  
T Endo ◽  
K Gunji ◽  
T Onaya
Keyword(s):  
Northern Blot Analysis ◽  
Thyroid Tissue ◽  
Human Thyroid ◽  
Graves Disease ◽  
Mrna Levels ◽  
Thyroid Cells ◽  
Normal Cells ◽  
Normal Thyroid ◽  
Filter Hybridization ◽  
Rat Thyroid

ABSTRACT We have cloned a cDNA whose mRNA levels are increased in malignantly transformed rat thyroid FRTL cells (FRTL-Tc cells). We constructed a cDNA library from FRTL-Tc cells in λgt10 and screened the cDNAs by differential plaque filter hybridization. Twenty-five thousand clones were screened and one cDNA (C140) was selected which corresponded to a mRNA whose expression was 5·8 times higher in FRTL-Tc cells than in FRTL cells. A 0·8 kb specific C140 mRNA was detected by Northern blot analysis of FRTL-Tc and FRTL mRNAs. The C140 cDNA was sequenced and found to encode a protein of 227 amino acids. We have found that C140 mRNA is conserved in human thyroid cells, but it is encoded by a smaller 0·7 kb transcript. C140 mRNA was highly expressed in neoplastic thyroid tissues and weakly in normal thyroid tissues in the same patients. Additionally, we found that C140 mRNA was also increased in the thyroid tissue of a patient with Graves' disease. These results suggest that C140 expression might be higher in rapidly growing thyroid cells than in normal cells, and might provide a new aspect for the study of thyroid tumours.

scholarly journals Association of Duoxes with Thyroid Peroxidase and Its Regulation in Thyrocytes

2010 ◽  
Vol 95 (1) ◽  
pp. 375-382 ◽  
Author(s):  
Yue Song ◽  
Jean Ruf ◽  
Philippe Lothaire ◽  
Didier Dequanter ◽  
Guy Andry ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Protein Kinase ◽  
Plasma Membranes ◽  
Cell Damage ◽  
Thyroid Tissue ◽  
Human Thyroid ◽  
Thyroid Peroxidase ◽  
Thyroid Cells ◽  
Hormone Synthesis ◽  
Thyroid Hormone Synthesis

Abstract Context: Thyroid hormone synthesis requires H2O2 produced by dual oxidases (Duoxes) and thyroperoxidase (TPO). Defects in this system lead to congenital hypothyroidism. H2O2 damage to the thyrocytes may be a cause of cancer. Objective: The objective of the study was to investigate whether Duox and TPO, the H2O2 producer and consumer, might constitute a complex in the plasma membrane of human thyroid cells, thus maximizing efficiency and minimizing leakage and damage. Design: The interaction between Duox and TPO was studied by coimmunoprecipitation and Western blotting of plasma membranes from incubated follicles prepared from freshly resected human thyroid tissue from patients undergoing thyroidectomy, and COS-7 cells transiently transfected with the entire Duoxes or truncated [amino (NH2) or carboxyl (COOH) terminal]. Results: The following results were reached: 1) Duox and TPO from membranes are coprecipitated, 2) this association is up-regulated through the Gq-phospholipase C-Ca2+-protein kinase C pathway and down-regulated through the Gs-cAMP-protein kinase A pathway, 3) H2O2 increases the association of Duox1 and Duox2 to TPO in cells and in membranes, and 4) truncated NH2- or COOH-terminal Duox1 and Duox2 proteins show different binding abilities with TPO. Conclusion: Coimmunoprecipitations show that Duox and TPO locate closely in the plasma membranes of human thyrocytes, and this association can be modulated by H2O2, optimizing working efficiency and minimizing H2O2 spillage. This association could represent one part of a postulated pluriprotein complex involved in iodination. This suggests that defects in this association could impair thyroid hormone synthesis and lead to thyroid insufficiency and cell damage.

The effects of cytokines, antithyroidal drugs and glucocorticoids on phagocytosis by thyroid cells

1988 ◽  
Vol 119 (3) ◽  
pp. 413-419 ◽  
Author(s):  
Mayumi Matsunaga ◽  
Katsumi Eguchi ◽  
Takaaki Fukuda ◽  
Hiroshi Tezuka ◽  
Yukitaka Ueki ◽  
...  
Keyword(s):  
Phagocytic Activity ◽  
Interleukin 1 ◽  
Thyroid Tissue ◽  
Interferon Α ◽  
Graves Disease ◽  
Dependent Manner ◽  
Normal Thyroid Tissue ◽  
Thyroid Cells ◽  
Latex Beads ◽  
Thyroid Glands

Abstract. The present study was undertaken to examine whether thyrocytes possess phagocytic activity and whether the phagocytic activity is influenced by cytokines, such as interleukin 1, 2 (IL 1, IL 2) and interferon-α, -β, and -γ (IFN-α, β, and γ), and drugs, such as methimazole and dexamethasone. Thyroid glands were obtained from patients with Graves' disease. Thyrocytes were prepared by collagenase digestion. Thyrocytes were pre-incubated in the presence or absence of cytokines and drugs at 37°C for 20 h and were further incubated with fluoresceinated latex beads at 37°C for 60 min. The number of phagocytic thyrocytes was determined by FACS IV. Phagocytosis of latex beads was indeed seen within thyrocytes and gradually increased in a time-dependent manner. The rate of phagocytosis in thyrocytes was extremely slow as compared with that in macrophages. Phagocytic activity was detected in thyrocytes from patients with Graves' disease and from normal thyroid tissue adjacent to thyroid cancer. Phagocytosis was inhibited by IL 1, but was enhanced by IL 2. Although the enhanced phagocytosis with IFN-β was consistently seen, little effect was detected with IFN-α and -γ. Both methimazole and dexamethasone markedly inhibited phagocytosis. These results indicated that thyrocytes had phagocytic properties and that their phagocytic activity was modulated by cytokines, antithyroidal drugs and dexamethasone.

scholarly journals Steroid receptor coactivator-1 interacts with NF-κB to increase VEGFC levels in human thyroid cancer

2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Bo Gao ◽  
Lingji Guo ◽  
Donglin Luo ◽  
Yan Jiang ◽  
Jianjie Zhao ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Tissue ◽  
Lymphatic Vessels ◽  
Steroid Receptor ◽  
Human Thyroid ◽  
Normal Thyroid Tissue ◽  
Normal Thyroid ◽  
Steroid Receptor Coactivator ◽  
Lymphatic Metastases ◽  
Factor C

Thyroid cancer is the most common endocrine cancer, and has a high incidence of lymphatic metastasis. Vascular endothelial growth factor C (VEGFC) is essential for development of lymphatic vessels and lymphatic metastases during carcinogenesis. Steroid receptor coactivator-1 (SRC-1) interacts with nuclear receptors and transcription factors to promote tumor proliferation and metastasis. However, the correlation between SRC-1 and VEGFC levels in the lymphatic metastases of thyroid cancer remains unclear. We analyzed 20-paired specimens of thyroid cancer tissue and normal thyroid tissue and found increased levels of SRC-1 and VEGFC proteins in 13/20 and 15/20 thyroid cancer specimens, respectively, when compared with those levels in specimens of normal thyroid tissue. A high level of SRC-1 expression was positively correlated with VEGFC and lymphatic endothelial cell marker LYVE-1 expression. Papillary thyroid carcinoma cell line TPC-1 displayed high levels of SRC-1 and VEGFC expression and was selected for stable knockdown of SRC-1 in vitro. Inhibition of SRC-1 significantly reduced the VEGFC levels in TPC-1 cells. We found that SRC-1 binds to transcription factor NF-kB (p50/p65), and that this coactivation complex directly promoted VEGFC transcription, which could be abrogated by SRC-1 knockdown. Up-regulated NF-kB signaling was also confirmed in thyroid cancer tissues. In vivo studies showed that SRC-1 knockdown restricted tumor growth, reduced the numbers of LYVE-1-positive lymphatic vessels, and decreased the levels of VEGFC in tumor tissues. These results suggest a tumorigenic role for SRC-1 in thyroid cancer via its ability to regulate VEGFC expression.

Intermediate microRNA expression profile in Graves’ disease falls between that of normal thyroid tissue and papillary thyroid carcinoma

2016 ◽  
Vol 70 (1) ◽  
pp. 33-39 ◽  
Author(s):  
Matthias Pohl ◽  
Florian Grabellus ◽  
Karl Worm ◽  
Georg Arnold ◽  
Martin Walz ◽  
...  
Keyword(s):  
Mirna Expression ◽  
Expression Profiles ◽  
Thyroid Tissue ◽  
Fold Change ◽  
Graves Disease ◽  
Papillary Thyroid ◽  
Normal Thyroid Tissue ◽  
Normal Thyroid ◽  
Significant Difference ◽  
Benign Thyroid

AimsMany studies have previously reported a higher prevalence of papillary thyroid carcinomas (PTC) in patients with Graves' disease (GD). MicroRNAs (miRNAs) are small, non-coding RNAs that are upregulated in PTC compared with benign thyroid tissue. The objective of the study was to examine the miRNA expression of selected miRNAs that are known to be upregulated in PTC in patients with GD.MethodsParaffin embedded thyroid tissue from 159 patients with GD was screened for expression of the miRNAs 146b, 181b, 21, 221 and 222 by RT-PCR. The expression profiles of four normal thyroids, 50 PTCs without concomitant GD and 11 patients with untreated GD served as the controls.ResultsThe expression pattern of these miRNAs in patients with GD is intermediate between that of benign thyroid tissue (p<0.001) and PTC (in three out of five miRNAs, p<0.001). This corresponds to a 15-fold change for GD versus PTC, and a 31-fold change for GD versus normal thyroid tissue. The miRNA expression in 11 papillary microcarcinomas found in our study (a prevalence of 0.07) was not different from that in PTC samples from patients without GD for four of five miRNA types. Furthermore, we found a significant difference in the expression of miRNA 221/222 between treated and untreated GD tissue.ConclusionsIn conclusion, we found an intermediate expression of specific miRNAs in thyroid tissue from patients with GD that fell between the expression levels found in normal thyroid glands and PTC, which suggests a possible influence of certain miRNAs on developing PTC in patients with GD.

scholarly journals Intracellular expression of reactive oxygen species-generating NADPH oxidase NOX4 in normal and cancer thyroid tissues

2010 ◽  
Vol 17 (1) ◽  
pp. 27-37 ◽  
Author(s):  
Urbain Weyemi ◽  
Bernard Caillou ◽  
Monique Talbot ◽  
Rabii Ameziane-El-Hassani ◽  
Ludovic Lacroix ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Biological Effects ◽  
Thyroid Tissue ◽  
Reactive Oxygen ◽  
Human Thyroid ◽  
Oxygen Species ◽  
Normal Thyroid Tissue ◽  
Normal Thyroid ◽  
Cellular Expression

NADPH oxidase 4 (NOX4) belongs to the NOX family that generates reactive oxygen species (ROS). Function and tissue distribution of NOX4 have not yet been entirely clarified. To date, in the thyroid gland, only DUOX1/2 NOX systems have been described. NOX4 mRNA expression, as shown by real-time PCR, was present in normal thyroid tissue, regulated by TSH and significantly increased in differentiated cancer tissues. TSH increased the protein level of NOX4 in human thyroid primary culture and NOX4-dependent ROS generation. NOX4 immunostaining was detected in normal and pathologic thyroid tissues. In normal thyroid tissue, staining was heterogeneous and mostly found in activated columnar thyrocytes but absent in quiescent flat cells. Papillary and follicular thyroid carcinomas displayed more homogeneous staining. The p22phox protein that forms a heterodimeric enzyme complex with NOX4 displayed an identical cellular expression pattern and was also positively regulated by TSH. ROS may have various biological effects, depending on the site of production. Intracellular NOX4–p22phox localization suggests a role in cytoplasmic redox signaling, in contrast to the DUOX localization at the apical membrane that corresponds to an extracellular H2O2 production. Increased NOX4–p22phox in cancer might be related to a higher proliferation rate and tumor progression but a role in the development of tumors has to be further studied and established in the future.

Protein composition in single follicles, homogenates and fine-needle aspiration biopsies from normal and diseased human thyroid

1981 ◽  
Vol 96 (3) ◽  
pp. 328-334 ◽  
Author(s):  
B. Anderberg ◽  
S. Eneström ◽  
J. Gillquist ◽  
B. Kägedal ◽  
J. C. Månsson ◽  
...  
Keyword(s):  
Thyroid Tissue ◽  
Protein Composition ◽  
Lithium Therapy ◽  
Protein Fractions ◽  
Human Thyroid ◽  
Lower Amount ◽  
Normal Thyroid Tissue ◽  
Nodular Goitre ◽  
Normal Thyroid ◽  
Thyroid Colloid

Abstract. The protein composition of the thyroid colloid was analysed by microgel electrophoresis and densitometry in 41 euthyroid patients. The colloid samples were obtained from single follicles by micropuncture, from homogenates of microbiopsies or from aspiration biopsies. Fourteen of the patients had morphologically normal thyroid tissue, 18 had atoxic nodular goitre and 9 of the patients had atoxic adenoma. Ten of the patients with nodular goitre had prior to the investigation recieved lithium therapy for psychiatric disorders. The main component of the thyroid colloid was 19S thyroglobulin (TG), but larger iodoproteins (S-TG) and smaller protein fractions, an albumin-like protein and a pre-albumin fraction, were also present in varying relative amounts. Analyses of homogenates of microbiopsies from normal thyroid tissue demonstrated the same protein composition as observed in single follicles. In colloid samples from atoxic nodular goitre the lighter protein fractions were absent in most of the samples. Analyses of homogenates or aspiration biopsies could not demonstrate this alteration in the protein composition in nodular goitre. Lithium therapy resulted in a significantly lower amount of the lighter protein fractions but unchanged amounts of the globulin fractions in atoxic nodular goitre. In the atoxic adenomas the protein composition was heterogeneous. The major globulin fractions as well as the lighter protein fractions were present in the analyses of colloids and homogenates of microbiopsies. Aspiration biopsies from atoxic adenomas could not be used for analyses of the protein composition due to contamination with serum proteins.

scholarly journals Expansion of inflammatory monocytes in periphery and infiltrated into thyroid tissue in Graves’ disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xinxin Chen ◽  
Yanqiu Wang ◽  
Yicheng Qi ◽  
Jiqi Yan ◽  
Fengjiao Huang ◽  
...  
Keyword(s):  
Thyroid Tissue ◽  
Graves Disease ◽  
Thyrotropin Receptor ◽  
Monocyte Subsets ◽  
Normal Thyroid Tissue ◽  
Normal Thyroid ◽  
Inflammatory Monocytes ◽  
B Cell Activating Factor ◽  
Thyrotropin Receptor Antibody

AbstractMonocytes are important mediators of immune system and are reported to be altered in autoimmune disorders. Little is known about the pathological role of monocytes in Graves’ disease (GD). Thus, we investigated monocytes in periphery and thyroid tissue in GD. Untreated GD patients were enrolled and followed up until remission. Monocytes were significantly increased and positively correlated with anti-thyrotropin receptor antibody (TRAb) in untreated GD (rcounts = 0.269, P < 0.001; rpercentage = 0.338, P < 0.001). Flow cytometry showed CD14++ CD16+ monocytes were increased and CD14++ CD16- monocytes were decreased in untreated GD (both P < 0.001). Skewed monocyte subsets were recovered in GD with remission. Serum B cell-activating factor (BAFF) was positively correlated with TRAb (r = 0.384 and P = 0.001). CD14++ CD16+ monocytes expressed higher level of BAFF in untreated GD (P < 0.05). The frequency of CD14+ monocytes and CD14+ CD16+ monocytes were significantly higher in GD thyroid tissue than in normal thyroid tissue (both P < 0.001). Our study suggested CD14++ CD16+ monocytes were significantly expanded and involved in the production of TRAb via secreting a higher level of BAFF in periphery. Besides, monocytes infiltrated into thyroid tissue and thus could serve as an important participant in GD pathogenesis.

scholarly journals Iodide Symporter Gene Expression in Human Thyroid Tumors1

1998 ◽  
Vol 83 (7) ◽  
pp. 2493-2496 ◽  
Author(s):  
Franco Arturi ◽  
Diego Russo ◽  
Martin Schlumberger ◽  
Jean-Antoine du Villard ◽  
Bernard Caillou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Thyroid Cancer ◽  
Cancer Patients ◽  
Differentiated Thyroid Cancer ◽  
Thyroid Tissue ◽  
Human Thyroid ◽  
Thyroid Peroxidase ◽  
Primary Cancer ◽  
Messenger Ribonucleic Acid ◽  
Nis Gene

Expression of the Na+/I− symporter (NIS) gene was investigated by RT-PCR in a selected series of 26 primary thyroid carcinomas (19 papillary, 5 follicular, and 2 anaplastic). Fifteen follicular adenomas (11 “cold ” and 4 “hot” adenomas) were also studied. Five of 19 papillary thyroid cancer did not express NIS messenger ribonucleic acid (mRNA). In all but 1 follicular cancer, NIS transcript was fully detected. In anaplastic tissue, NIS mRNA was only barely detected in 1 case. All of the follicular thyroid adenomas except 1 expressed the NIS gene. In contrast, all tumors studied excluding the anaplastic histotype fully expressed thyroglobulin and thyroid peroxidase mRNA transcripts. In 2 patients, a lower expression (3- to 5-fold) of NIS mRNA was found in metastasis by dot blot analysis compared with those in both normal and primary neoplastic thyroid tissue. Four of 8 differentiated thyroid cancer patients selected for the presence of metastases with negative posttherapy 131I total body scan showed the lack of NIS gene expression in their primary cancer. This defect, at least in these cases, is a somatic and intrinsic lesion of the primary cancer cells and is not due to a dedifferentiation process in the metastatic tissue. The early detection of the loss of NIS gene expression in the primary cancer, therefore, may provide useful information for the management of differentiated thyroid cancer patients.

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