Thyroid Peroxidase Expression Research Articles

Canine follicular cell and medullary thyroid carcinomas: Immunohistochemical characterization

Research on modulation of iodine uptake by thyroid cells could help improve radioiodine treatment of dogs with thyroid tumors. The aim of this study was to characterize the immunohistochemical expression of thyroid transcription factor-1 (TTF-1), thyroglobulin, thyrotropin receptor (TSHR), sodium iodide symporter (NIS), pendrin, thyroid peroxidase (TPO), vimentin, and Ki-67 in follicular cell thyroid carcinomas (FTCs) and medullary thyroid carcinomas (MTCs), and to compare protein expression between FTC causing hyperthyroidism and FTC of euthyroid dogs. Immunohistochemistry was performed in 25 FTCs (9 follicular, 8 follicular-compact, and 8 compact) and 8 MTCs. FTCs and MTCs were positive for TTF-1, and expression was higher in FTCs of euthyroid dogs compared with FTCs of hyperthyroid dogs ( P= .041). Immunolabeling for thyroglobulin was higher in follicular and follicular-compact FTCs compared with compact FTCs ( P = .001), while vimentin expression was higher in follicular-compact FTCs compared with follicular FTCs ( P = .011). The expression of TSHR, NIS, pendrin, and TPO was not significantly different among the different subtypes of FTCs or between FTCs causing hyperthyroidism and FTCs in euthyroid dogs. TSHR, NIS, pendrin, and TPO were also expressed in MTCs. Ki-67 labeling index was comparable between FTCs and MTCs, and between FTCs causing hyperthyroidism and FTCs in euthyroid dogs. Proteins of iodine transport were also expressed in canine MTCs, which could have implications for diagnosis and treatment. The different expression of thyroglobulin and vimentin between FTC histological subtypes could reflect variations in tumor differentiation.

TPO Gene Expression in Relation with Promoter SNPs in Iraqi Patients with Hyperthyroidism

Background: Thyroid peroxidase (TPO) gene mutations are one of the most common causes of thyroid disorders. Objective: To investigate the effect of genetic polymorphisms in the TPO promoter region on gene expression in early-diagnosed hyperthyroid patients. Methods: Genomic DNA was extracted from 100 blood samples (75 hyperthyroid patients and 25 healthy controls), then the TPO promoter region was amplified and sequenced for genotyping rs2071399, rs2071400, and rs2071403 SNPs. Total RNA was also isolated, and cDNA synthesis was performed to determine quantitatively the expression of TPO by using qPCR. The level of TPO antibodies in serum was determined by using an enzyme-linked immunosorbent assay (ELISA). Results: The prevalence of hyperthyroidism in women was significantly higher than in men, as were serum levels of TPO-Abs. There was a significant increase in serum TPO-Abs in hyperthyroid patients (235.29 IU/ml) compared with healthy controls. Genotypes of three SNPs (rs2071399 G/A, rs2071400 C/T, and rs2071403 A/G) in the TPO promoter region were TPO rs2071399 AG and GG, and rs2071400 CT and TT genotypes were more frequent in hyperthyroid patients. There are no significant differences between rs2071403 polymorphic and non-polymorphic genotypes among hyperthyroid patients and healthy controls. The rs2071399 G/A and rs2071400 C/T gene promoter polymorphism significantly down-regulated constitutive TPO gene expression in hyperthyroid patients, but rs2071403 A/G has no major effect on gene expression. Conclusion: There was an association between the mutation in the promoter region of TPO and the incidence of hyperthyroidism.

Iodine avidity in papillary and poorly differentiated thyroid cancer is predicted by immunohistochemical and molecular work-up.

Successful radioiodine treatment of differentiated thyroid cancer requires iodine avidity: that is, the concentration and retention of iodine in cancer tissue. Several parameters have previously been linked with lower iodine avidity. However, a comprehensive analysis of which factors best predict iodine avidity status, and the magnitude of their impact, is lacking. Quantitative measurements of iodine avidity in surgical specimens (primary tumour and lymph node metastases) of 28 patients were compared to immunohistochemical expression of the thyroid-stimulating hormone receptor, thyroid peroxidase (TPO), pendrin, sodium-iodide symporter (NIS) and mutational status of BRAF and the TERT promoter. Regression analysis was used to identify independent predictors of poor iodine avidity. Mutations in BRAF and the TERT promoter were significantly associated with lower iodine avidity for lymph node metastases (18-fold and 10-fold, respectively). Membranous NIS localisation was found only in two cases but was significantly associated with high iodine avidity. TPO expression was significantly correlated with iodine avidity (r = 0.44). The multivariable modelling showed that tumour tissue localisation (primary tumour or lymph node metastasis), histological subtype, TPO and NIS expression and TERT promoter mutation were each independent predictors of iodine avidity that could explain 68% of the observed variation of iodine avidity. A model based on histological subtype, TPO and NIS expression and TERT promoter mutation, all evaluated on initial surgical material, can predict iodine avidity in thyroid cancer tissue ahead of treatment. This could inform early adaptation with respect to expected treatment effect.

TPO as an indicator of lymph node metastasis and recurrence in papillary thyroid carcinoma

The objective of this study was to investigate the expression of thyroid peroxidase (TPO) in papillary thyroid carcinoma (PTC) and to preliminarily investigate its value as a marker of lymph node metastasis and recurrence in patients with PTC. Clinical data of PTC patients and TPO expression were collected from The Cancer Genome Atlas (TCGA) database for analysis. We recruited 230 consecutive PTC patients from the Department of Thyroid Surgery of the First Affiliated Hospital of Kunming Medical University, collected their clinicopathological data, and also performed immunohistochemical analysis of TPO expression on their thyroid specimens to validate the results of bioinformatics analysis. In addition, the construction of protein–protein interaction networks was performed too. Functional enrichment analysis and immuno-infiltration analysis characterized the pathways in which TPO genes may be involved. Data mining based on the TCGA database showed that TPO expression in PTC tissues was significantly lower than in paired normal thyroid tissues. The expression level of TPO in PTC tissues correlated with tumor lymph node metastasis and recurrence. Follow-up data from our center also validated the difference in TPO expression and its relationship with lymph node metastasis in PTC patients. Functional enrichment analysis showed that TPO function was significantly associated with signaling pathways related to amino acid metabolism, gene expression regulation and tumorigenesis. TPO expression was also significantly associated with immune infiltration. Our study showed that reduced TPO expression was significantly associated with lymph node metastasis and recurrence in patients with PTC, and we validated this result in our central cohort. These data suggest that TPO may serve as a prognostic indicator for PTC.

Thyroid-Disrupting Effects of Exposure to Fipronil and Its Metabolites from Drinking Water Based on Human Thyroid Follicular Epithelial Nthy-ori 3-1 Cell Lines.

Fipronil is a broad-spectrum insecticide used for plants and poultry. Owing to its widespread use, fipronil and its metabolites (fipronil sulfone, fipronil desulfinyl, and fipronil sulfide), termed FPM, can be frequently detected in drinking water and food. Fipronil can affect the thyroid function of animals, but the effects of FPM on the human thyroid remain unclear. We employed human thyroid follicular epithelial Nthy-ori 3-1 cells to examine combined cytotoxic responses, thyroid-related functional proteins including the sodium-iodide symporter (NIS), thyroid peroxidase (TPO), deiodinases I-III (DIO I-III), and the nuclear factor erythroid-derived factor 2-related factor 2 (NRF2) pathway induced by FPM of 1-1000-fold concentrations detected in school drinking water collected from a heavily contaminated area of the Huai River Basin. Thyroid-disrupting effects of FPM were evaluated by examining biomarkers of oxidative stress and thyroid function and tetraiodothyronine (T4) levels secreted by Nthy-ori 3-1 cells after FPM treatment. FPM activated the expression of NRF2, HO-1 (heme oxygenase 1), TPO, DIO I, and DIO II but inhibited NIS expression and increased the T4 level of thyrocytes, indicating that FPM can disrupt the function of human thyrocytes through oxidative pathways. Given the adverse impact of low FPM concentrations on human thyrocytes, supportive evidence from rodent studies, and the critical importance of thyroid hormones on development, the effects of FPM on the neurodevelopment and growth of children warrant priority attention.

Effects Study of Some Common Food Additives on Gene Expression of TPO Gene in Young Male Rats

This study was conducted in an animal house / Department of biology / Al-Qadisiyah University from November 2021 to February 2022, To study the effect of food additives on gene expression Thyroid Peroxidase (TPO) for the thyroid gland This study included 32 young male rats, It was randomly divided into four equal groups, The control group, which dosed 1 ml of normal drinking water for the duration of the experiment and for a period of 30 days, The first treatment group (T1) dosed tetrazine dye at a concentration of 25 mg / kg of body weight for 30 days, The second treatment group (T2) was dosed with chocolate brown dye HT at a concentration of 200 mg / kg of body weight during the 30-day trial period, The third treatment group (T3), which was dosed with the preservative sodium benzoate at a concentration of 25 mg / kg of body weight during the 30-day trial period. The results of the statistical analysis of the molecular study of the gene expression of the enzyme thyroid peroxidase(TPO) No significant change (p >0.05) In the first group (T1) , second group (T2) And the third group (T3) when compared to the control group. And there was a significant increase (p<0.05) in the third group (T3) compared to the first group (T1) and the second (T2). On the other hand, the results of the immunohistochemistry study of the immune reaction showed the presence of TPO enzyme in the cytoplasm and tops of the follicular cells of the thyroid gland in the control group, and the intensity of (TPO) immunostaining was high in the mentioned sites. s for the first treatment group (T1) and the second treatment group (T2), the immune reaction was weak, meaning that the (TPO) enzyme was absent its gene expression disappeared or decreased in the cytoplasm and the tops of the membranes of the vesicular cells of the thyroid gland. The results of the third treatment group (T3) also indicated that it retained the dye because the strength of the immunostaining of the enzyme (TPO) was clear, but with a lower intensity than the control group. (TPO) gene expression was present in the cytoplasm and tops of the follicular cells of this group, but less than that of the control group. We conclude that the additives have negative effects on the expression of the enzyme (TPO) enzyme, as they lead to a defect in the function of the thyroid gland and should be minimized, especially in children's food containing it. Keyword: thyroid gland, immunnohistochemical ,tartrazine , benzoatsodium, chocolatebrown HT E 155, expression of TPO

Validation of Immunohistochemistry for Canine Proteins Involved in Thyroid Iodine Uptake and Their Expression in Canine Follicular Cell Thyroid Carcinomas (FTCs) and FTC-Derived Organoids.

Thyrotropin receptor (TSHR), sodium iodide symporter (NIS), pendrin, and thyroid peroxidase (TPO) are essential for the uptake of iodine by follicular thyroid cells. The aim of this study was to establish immunohistochemistry (IHC) protocols for TSHR, NIS, pendrin, and TPO in canine tissues and characterize their expression in organoids derived from canine follicular cell thyroid carcinoma (FTC) and in the respective primary tumors. This constitutes a fundamental step to establish organoids as a model to study the uptake of iodine in canine FTC. Commercially available antibodies directed against human proteins were selected. Antibody specificity was confirmed by western blot using lysates of the HTori-3 human thyroid cell line and healthy canine thyroid gland. IHC was validated using HTori-3 cells and a set of canine normal tissues including healthy thyroid gland. The expression of TSHR, NIS, pendrin, and TPO was evaluated in 3 organoid lines derived from FTC and respective primary tumors. All 4 antibodies produced specific bands by western blot and cytoplasmic labeling in follicular cells by IHC in both human HTori-3 cells and canine thyroid gland. NIS also showed basolateral membrane immunolabeling in follicular cells. All 4 proteins were highly expressed in organoids derived from FTC. The expression was similar or higher compared to the primary tumors. The results of this study characterize organoids derived from canine FTC as a suitable in vitro model to investigate iodine uptake, opening new research possibilities in the field of canine thyroid cancer therapy.

Clinical implications of TPO and AOX1 in pediatric papillary thyroid carcinoma.

BackgroundThyroid carcinoma is a common pediatric head and neck cancer, of which papillary thyroid cancer (PTC) is the most common type. Previously, we found that thyroid peroxidase (TPO) and aldehyde oxidase 1 (AOX1) were differentially expressed in PTC. This study explored the clinical importance of TPO and AOX1 in the diagnosis and prognosis of PTC in children.MethodsBoth TPO and AOX1 expression in PTC were analyzed using datasets from Gene Expression Omnibus (GEO). TPO and AOX1 protein levels in plasma from patients with PTC and non-tumor controls were detected via enzyme-linked immunosorbent assay (ELISA). The diagnostic accuracy of TPO and AOX1 was assessed using receiver operating characteristic (ROC) curve analysis. The association between gene expression levels and patient survival was explored using the Kaplan-Meier plotter online database.ResultsThe results revealed that TPO and AOX1 expression was significantly downregulated in four independent datasets (GSE33630, GSE27155, GSE3678, and GSE3467). TPO and AOX1 protein levels in blood plasma were significantly decreased in patients with PTC. Quantitative analysis demonstrated that TPO and AOX1 levels in plasma had satisfactory predictive performance and the ability to discriminate PTC from healthy samples. Prognostic analysis demonstrated that low levels of TPO and AOX1 were markedly associated with poor survival in patients with PTC.ConclusionsIn summary, these results implied that TPO and AOX1 could serve as novel biomarkers for the diagnosis and prognosis of pediatric PTC.

Transcriptome analysis of the effect of diosgenin on autoimmune thyroiditis in a rat model

In a mouse model of Graves’ disease (GD), diosgenin has been shown to have a therapeutic effect on GD by alleviating goitre. However, research on the effect of diosgenin on autoimmune thyroiditis (AIT) is lacking. In this study, transcriptomics was used to comprehensively analyse the protective effect of diosgenin against AIT in rats and the possible mechanism. The results showed that in the diosgenin-intervention group, compared to the model group, the expression of serum triiodothyronine, thyroxine, free triiodothyronine, and free thyroxine was decreased and that of thyroid-stimulating hormone was increased; these changes were accompanied by the downregulation of thyroglobulin, TSH receptor antibody and thyroid peroxidase expression in serum. Furthermore, transcriptome detection, RT-qPCR and immunohistochemistry verification revealed that in thyroid tissue, the relative mRNA and protein expression of cyclic adenosine 3′,5′-monophosphate (cAMP), protein kinase A (PKA) and cAMP response element-binding protein (Creb) were increased and the mRNA expression of S100 calcium-binding protein A9 (S100A9) was decreased in the diosgenin groups. In summary, diosgenin alleviates the development of AIT, possibly via the activation of the cAMP/PKA/Creb pathway and downregulation of S100A9 gene expression.

Thyroid peroxidase in human endometrium and placenta: a potential target for anti-TPO antibodies.

Autoimmune thyroid disease is the most common endocrine disorder during pregnancy. Thyroid autoantibodies (TAs) have been suggested to serve a role in implantation failure and spontaneous abortion. Until now, there are no data on the potential interaction of TAs with human reproductive organs. Here, we set out for the first time to test this hypothesis by studying the expression of thyroid peroxidase (TPO) at gene and protein level in human reproductive organs. Endometrial samples were taken from normal women, and placenta tissues were collected after full-term caesarian section. Expression of TPO messenger RNA (mRNA) was investigated by qRT-PCR. In addition, polyclonal anti-TPO antibodies were produced and the expression of TPO protein in mentioned tissues was evaluated by immunohistochemistry and Western blot analysis. The reactivity of anti-TPO antibody in human embryos was evaluated by immunofluorescent staining. For the first time, our study showed that TPO is expressed at gene and protein levels in endometrium and placenta. TPO expression was mainly localized to glandular and luminal epithelial cells in the endometrium. In placenta, the syncytiotrophoblasts and invasive trophoblast cells were the main cell types that expressed TPO protein. Specific band of approximately 110kDa was observed in all endometrial and placental tissues by Western blot analysis. However, no expression of TPO protein was observed in human embryo. TPO expression in endometrium and placenta may explain higher frequency of abortion and infertility in patients with thyroid autoimmunity.

Effects of butylparaben exposure on thyroid peroxidase (TPO) and type 1 iodothyronine deiodinase (D1) in female Wistar rats

Endocrine disrupting chemicals (EDCs) have been considered as one of the major contributors of growing burden of thyroid disorders across the globe, and most of these chemicals have the potential to disrupt thyroid hormones (THs) synthesis and other regulatory pathways of thyroid gland function. Butylparaben (BP), an established xenobiotic used as synthetic preservative, has not been thoroughly evaluated for its molecular mechanism of thyroid disrupting potential. We investigated the effects of BP on activity and gene expression of thyroid peroxidase (TPO) and type 1 iodothyronine deiodinase (D1) in female Wistar rats following subcutaneous exposure to BP at doses of 1, 5 and 10 mg/kg BW/day (expressed as BP1, BP5 and BP10 respectively) for 7 and 21 days. The results showed that BP1 and BP5 significantly increased serum T3/T4 ratio and TSH level, while BP10 reduced the level of T4 significantly without any apparent consequences on TSH and T3 levels. TPO activity in thyroid was significantly increased (p < 0.05) at BP1 and BP5, but BP10 treatment showed no effect like 17β-estradiol (E2). After 7 days of exposure, BP reduced D1 activity in kidney in a dose-dependent manner, while decrease in D1 activity was significant only after dosing with BP1 for 21 days (p < 0.05). Moreover, 7 and 21 days of BP exposure caused significant fold increase of Tpo mRNA levels in thyroid. In kidney, BP down-regulated the Dio1 gene (encodes D1) expression after 7 days, but significant fold increase was observed following 21 days of treatment. In conclusion, the present study revealed that BP exposure altered the transcriptional expression and activity of TPO and D1, where TSH reinforced possible association with TPO activity.

Application of Thyroid Peroxidase (TPO) and Hector Battifora Mesothelial-1 (HBME-1) immunohistochemical markers in the diagnosis of papillary thyroid carcinoma of the thyroid

Background: Thyroid cancer is the most common endocrine malignancy accounting for >90% of malignancies of endocrine glands. The inter and intraobserver variation in the histomorphological diagnosis of Papillary Thyroid Carcinomas may sometimes pose a diagnostic difficulty. Application of IHC biomarkers may play an active or complementary role in their accurate classification. Aim: The present study was conducted to evaluate if HBME-1 and TPO immunohistochemical analysis can reliably differentiate papillary carcinomas from other thyroid lesions. Material and Methods: 50 cases of benign and malignant thyroid lesions were taken. Immunohistochemical staining for HBME-1 and TPO was performed. HBME-1 and TPO score was interpreted as absent and positive. Medical records were retrieved and their clinical data, surgical treatment, and pathological findings were noted. Results: Out of 50 cases, 19 (73.1%) cases were diagnosed PTC, 4 (15.4%) cases were FTC, 3(11.5%) cases were of MTC and 24 cases of benign thyroid lesions. TPO expression was found positive in 91.7% of cases of Benign thyroid lesions. In malignant thyroid lesions, negative expression of TPO was seen in 63.16%, 0% and 33.33% of PTC, FCT, and MCT respectively. HBME-1 showed negative expression in 83.3% of cases of benign thyroid lesions. Whereas, in malignant thyroid lesion HBME-1 expression was positive in 78.95%, 50% and 0% cases of PTC, FCT, and MCT respectively. Conclusion: Testing for expression of HBME-1 has been shown to improve the diagnostic accuracy for thyroid malignant nodules. The combination of HBME-1, and TPO may contribute to an accurate diagnosis of papillary thyroid carcinoma.

Ультразвукові та цитологічні характеристики радіойодчутливості метастазів папілярного раку щитоподібної залози

Мета — дослідження ультразвукових і цитологічних характеристик метастазів, виявлених у поопераційний період, залежно від їх йоднакопичувальної здатності. Матеріал і методи. Ультразвукові, цитологічні, імуноцитохімічні дослідження проводили на групі метастазів папілярного раку щитоподібної залози, виявлених у поопераційний період (після тиреоїдектомії та радіойодтерапії): 30 радіойодчутливих метастазів і 65 радіойодрезистентних. Оцінювали такі ультразвукові характеристики, як локалізація метастазів, чи є вони множинними або поодинокими, ехогенність, ехоструктуру та наявність гіперехогенних включень. Цитологічні та імуноцитохімічні дослідження проводили на пункційному матеріалі даних метастазів, забарвленому за Романовським. Використовували непрямий імунопероксидазний метод із моноклональними антитілами до тиреоїдної пероксидази та тиреоглобуліну. Статистичний аналіз проводили за непараметричним критерієм Манна – Уїтні та методом χ2 у програмі Statistica 11.0. Результати. Проведені дослідження ультразвукових і цитологічних характеристик поопераційних метастазів папілярних карцином щитоподібної залози не виявили значущої різниці між групами радіойодрезистентних і радіойодчутливих метастазів за такими ультразвуковими характеристиками, як ехогенність, ехоструктура та наявність гіперехогенних включень. Показано, що у випадках виявлення гіпоехогенних метастазіву латеральних лімфатичних колекторах імовірність радіойодрезистентності метастазів становить 93±2%. Ультразвукову ознаку кістозної дегенерації виявляли в 1,8 раза частіше в радіойодрезистентних метастазах порівняно з радіойодчутливими. Цитологічні дослідження демонструють фенотипову гетерогенность епітелію радіойодрезистентних метастазів порівняно з радіойодчутливими та вірогідну різницю в експресії тиреоглобуліну й тиреоїдної пероксидази. Висновки. За даними ультразвукового дослідження не виявлено достовірних змін, які дозволили б проводити диференційну діагностику між радіойодрезистентними та радіойодчутливими метастазами папілярного раку щитоподібної залози. Визначено цитологічні ознаки радіойодрезистентних метастазів папілярного тиреоїдного раку, які дозволяють їх передопераційне прогнозування. Продемонстровано значущу редукцію експресії тиреоїдної пероксидази та тиреоглобуліну в пунктатах радіойодрезистентних метастазів порівняно з радіойодчутливими, що є підставою передопераційного прогнозування радіойодрезистентності поопераційних метастазів папілярного тиреоїдного раку. Виявлені за даними ультразвукової діагностики метастатичні лимфатичні вузли шиї дозволяють проводити подальші імуноцитохімічні та цитологічні дослідження, що може підвищити ефективність діагностики метастазів високодиференційованого раку щитоподібної залози й полегшити вибір подальшого лікування.

Expression of pendrin and NIS iodide transporters in human breast tumor and peri-tumoral tissue.

IntroductionThyroid iodide transporters, Na+/I– symporter (NIS) and pendrin (PDS), are responsible for supplying this vital micronutrient for thyroid hormone synthesis by thyroid peroxidase (TPO). Both proteins were shown to be expressed, apart from the thyroid, also in other human tissues, including lactating mammary gland. NIS expression in human breast cancers has been widely studied. On the other hand, until now PDS mRNA levels in breast tumor tissue have been estimated only in high throughput analyses. Previously, we have observed that TPO is expressed in normal and cancerous human breast tissues and shows enzymatic activity. However, biochemical activity of TPO in human breast cancer cells requires iodide transport by NIS and PDS. Therefore, to extend our previous study on TPO expression and function in human breast tumors we performed analysis of NIS and PDS levels in the same group of patients.Material and methodsThe study involved detection of NIS and PDS protein levels by immunohistochemistry and Western blotting, as well as mRNA levels by real-time quantitative polymerase chain reaction.ResultsHere we provide direct evidence that NIS and PDS are expressed in human breast cancer tissue, with NIS levels being increased and PDS levels decreased in tumor tissue. Interestingly, PDS mRNA levels in breast cancer tissue seem to be influenced by the estrogen receptor status and age of the patients, while NIS mRNA levels were dependent on histological type of the tumor.ConclusionsThis study provides valuable information important for consideration in diagnostic or therapeutic application of radioiodine in breast cancer management.

Combined use of galectin-3 and thyroid peroxidase improves the differential diagnosis of thyroid tumors.

The differential diagnosis of well-differentiated tumors of follicular cell origin remains the most problematic task in thyroid pathology. Specific morphologic criteria (capsular and/or vascular invasion, nuclear characteristics) are crucial in the diagnosis of these neoplasms. However, the assessment of malignant features is inconclusive in some cases. Moreover, oncocytic thyroid tumors remain controversial in a respect to their pathobiology, behavior and management. Therefore, the useful diagnostic/prognostic thyroid markers are awaited. The aim of our study was to evaluate the expression of galectin-3 and thyroid peroxidase (TPO) in benign and malignant thyroid tumors of follicular cell origin. A total of 186 archival thyroid samples including 38 non-oncocytic follicular adenomas, 53 oncocytic (Hürthle cell) adenomas, 6 non-oncocytic follicular carcinomas, 23 oncocytic (Hürthle cell) carcinomas, 43 non-oncocytic papillary carcinomas, and 23 oncocytic papillary carcinomas were analyzed for galectin-3 and TPO expression by immunohistochemistry. Both types of papillary carcinomas showed significant upregulation of galectin-3 in comparison with the other tumor types, likewise, significant differences in galectin-3 expression were discovered between non-oncocytic and oncocytic variants of studied tumors excluding follicular carcinoma. Significant lowering of TPO was revealed in oncocytic adenomas and papillary carcinomas. In conclusion, the combined use of galectin-3 and TPO markers could help to improve the differential diagnosis of thyroid tumors. Differences in the galectin-3 and TPO expression between some oncocytic and non-oncocytic tumors support their separation in the latest WHO classification of thyroid tumors.

Allylpyrocatechol, isolated from betel leaf ameliorates thyrotoxicosis in rats by altering thyroid peroxidase and thyrotropin receptors

Allylpyrocatechol (APC) was isolated from betel leaf and its possible role in L-thyroxin (L-T4)-induced thyrotoxic rats was evaluated. The disease condition, thyrotoxicosis was confirmed by higher levels of thyroid hormones and low thyrotropin (TSH) in serum. Increased hepatic activities of 5′-mono-deiodinase(5′D1), glucose-6-phospatase (G-6-Pase); serum concentrations of alanine transaminase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase(LDH) and tumour necrosis factor-alpha(TNF-α) were observed in thyrotoxic rats. Hepatic lipid peroxidation(LPO) was also increased and the endogenous antioxidants were depleted in these rats. In western blot analysis thyroid peroxidase expression was found to be reduced, whereas thyrotropin receptor(TSHR) expression was enhanced in thyroid gland of these animals. On the other hand, APC treatment in thyrotoxic rats decreased the levels of serum thyroid hormones, ALT, AST, TNF-α and LDH, as well as hepatic 5′ D1 and G-6-Pase activities. However, it increased the serum TSH levels. APC also reduced the hepatic LPO and increased the cellular antioxidants in thyrotoxic rats. However, expression of TSHR was inhibited and TPO was increased by APC. The test compound also improved histological features in both liver and thyroid. Present report appears to be the first one that indicates the positive role of APC in ameliorating T4-induced thyrotoxicosis.

Цитологічні особливості багаторазово метастазуючих тиреоїдних папілярних карцином

Мета — комплексне цитологічне та імуноцитохімічне дослідження тиреоцитів пунктатів поопераційних реґіонарних метастазів папілярних тиреоїдних карцином із багаторазовим метастазуванням і порівняльний аналіз цитологічних характеристик первинних і повторних поопераційних метастазів у кожного пацієнта. Матеріал і методи. Цитоморфологічні та імуноцитохімічні дослідження з використанням моноклональних антитіл проти тиреоїдної пероксидази, тиреоглобуліну, антигену Кі‑67 проводили на матеріалі тонкоголкових аспіраційних пункційних біопсій 26 метастазів, виявлених у поопераційний період (після проведення тиреоїдектомії та радіойодтерапії), отриманих від 12 хворих на папілярний тиреоїдний рак із багаторазовим метастазуванням. Результати. За результатами дослідження фенотипових характеристик тиреоцитів пунктатів метастазів рецидивуючих папілярних карцином щитоподібної залози з повторним метастазуванням виявлено зміни цитологічних та імуноцитохімічних характеристик тиреоцитів у пунктатах повторних метастазів порівняно з такими первинних метастазів. Показано вірогідне зниження експресії тиреоїдної пероксидази та тиреоглобуліну та появу фенотипової гетерогенності популяції тиреоцитів (світлі клітини, клітини з макулами, оксифільні клітини) повторних метастазів порівняно з первинними. Висновок. У клітинах метастазів рецидивуючих папілярних карцином із повторним метастазуванням виявлено втрату ознак диференціації — вірогідне зниження експресії тиреоїдної пероксидази та тиреоглобуліну та появу фенотипової гетерогенності популяції тиреоцитів.

Chavibetol corrects thyrotoxicosis through alterations in thyroid peroxidase

Thyrotoxicosis is a clinical syndrome that commonly results from excess secretion and/or release of thyroid hormones in the circulation. It affects most of the body systems and if not treated properly may lead to serious health problems. In this investigation, we isolated a phenolic compound, chavibetol (CHV) from Piper betel leaf and evaluated its possible ameliorative effects in thyrotoxicosis of rats. Adult female rats were rendered thyrotoxic by the administration of L-thyroxine (L-T4) at 500μg/kg/day, i.p., for 12days, and then chavibetol (20.0mg/kg, p.o.) was administered for 2weeks. L-T4 administration elevated the concentration of serum thyroxine and triiodothyronine, activities of alanineaminotransferase and aspartate aminotransferase, and decreased the thyrotropin level as well as the expression of thyroid peroxidase (TPO). Further, it increased the activities of hepatic 5'mono-deiodinase-I, glucose-6--phosphatase, sodium-potasium-ATPase, and lipid peroxidation, and depleted the cellular antioxidants. However, chavibetol treatment to thyrotoxic rats normalized almost all these indices including TPO and also preserved the integrity of thyroid tissues suggesting its potential to correct thyrotoxicosis. Effects of CHV were more or less similar to a conventional antithyroid drug, propylthiouracil (PTU).

Biochemical properties of thyroid peroxidase (TPO) expressed in human breast and mammary-derived cell lines.

Thyroid peroxidase (TPO) is an enzyme and autoantigen expressed in thyroid and breast tissues. Thyroid TPO undergoes a complex maturation process however, nothing is known about post-translational modifications of breast-expressed TPO. In this study, we have investigated the biochemical properties of TPO expressed in normal and cancerous human breast tissues, and the maturation process and antigenicity of TPO present in a panel of human breast tissue-derived cell lines. We found that the molecular weight of breast TPO was slightly lower than that of thyroid TPO due to decreased glycosylation and as suggest results of Western blot also shorter amino acid chain. Breast TPO exhibit enzymatic activity and isoelectric point comparable to that of thyroid TPO. The biochemical properties of TPO expressed in mammary cell lines and normal thyrocytes are similar regarding glycan content, molecular weight and isoelectric point. However, no peroxidase activity and dimer formation was detected in any of these cell lines since the majority of TPO protein was localized in the cytoplasmic compartment, and the TPO expression at the cell surface was too low to detect its enzymatic activity. Lactoperoxidase, a protein highly homologous to TPO expressed also in breast tissues, does not influence the obtained data. TPO expressed in the cell lines was recognized by a broad panel of TPO-specific antibodies. Although some differences in biochemical properties between thyroid and breast TPO were observed, they do not seem to be critical for the overall three-dimensional structure. This conclusion is supported by the fact that TPO expressed in breast tissues and cell lines reacts well with conformation-sensitive antibodies. Taking into account a close resemblance between both proteins, especially high antigenicity, future studies should investigate the potential immunotherapies directed against breast-expressed TPO and its specific epitopes.

Sex Differences in the Production of SLC5A5, Thyroid Peroxidase, and Thyroid Hormones in Pubertal Rats Exposed to Endocrine Disruptor Dichlorodiphenyltrichloroethane (DDT) during Postnatal Ontogeny.

Sex differences in the expression of iodide transporter SLC5A5 and thyroid peroxidase in thyroid follicular epithelium and thyroid serum profile were assessed in pubertal rats exposed to endocrine disruptor DDT starting from the first postnatal day. It was found that exposure to DDT reduced expression of SLC5A5 in peripheral regions of thyroid lobes in males and in central regions in females. The most pronounced sex differences were observed in thyroid peroxidase expression that remained sensitive to thyroid stimulating hormone regulation in males and lost sensitivity to pituitary stimulation in females after exposure to disruptor, which determines more pronounced hypothyroidism in females.