المؤلفون: María Eugenia Gonsebatt Bonaparte, E Rios-Sanchez, Alberto González-Zamora, María Fernanda González-Delgado, Rebeca Pérez-Morales, Alejandra Zámago Amaro, Elizabeth Meza Mata

المصدر: Environmental Toxicology. 36:2380-2391

مصطلحات موضوعية: endocrine system, medicine.medical_specialty, biology, Chemistry, Health, Toxicology and Mutagenesis, Thyroid, Dual oxidase 2, General Medicine, Pendrin, Management, Monitoring, Policy and Law, Toxicology, Endocrinology, medicine.anatomical_structure, Thyroid peroxidase, Internal medicine, Symporter, medicine, biology.protein, Endocrine system, Receptor, Hormone

الوصف: Nitrates are natural compounds present in soil and water; however, the intense use of fertilizers has increased their presence in groundwater with deleterious effects on human health. There is evidence of nitrates acting as endocrine disruptors; however, the underlying molecular mechanisms have not been fully described. Here, we investigated the effect of subchronic exposure to different concentrations of sodium nitrate in female Wistar rats, evaluating thyroid hormonal parameters, such as Nis transporter (Na+ /I- symporter, Slc5a5) and Tsh-R receptor protein expression, as well as transcription of the Tpo (thyroperoxidase), Tg (tiroglobulin), Duox2 (dual oxidase 2), Pds (pendrin), and Mct8 (Mct8 transporter, Slc16a2) genes. Hematological and histochemical changes in the liver and thyroid were also explored. Significant differences were found in platelet and leukocyte counts; although a significant increase in the weight of the thyroid gland was observed, no differences were found in the levels of the hormones Tsh, T3, and T4, but a modulation of the mRNA expression of the Tg, Tpo, Duox2, Mct8, and Pds genes was observed. Morphological changes were also found in liver and thyroid tissue according to the exposure doses. In conclusion, subchronic exposure to sodium nitrate induces leukocytosis consistent with an inflammatory response and upregulation of Sod2 in the liver and increases the expression of genes involved in the synthesis of thyroid hormones, keeping thyroid hormone levels stable. Histological changes in the thyroid gland suggest a goitrogenic effect.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::4fb7ca12f16117e326dd0cf4ab52c37bTest
https://doi.org/10.1002/tox.23351Test

المؤلفون: Claudia Viggiano, Gianluca Lista, Valeria Calcaterra, Luigina Spaccini, Rossella Lamberti, Gian Vincenzo Zuccotti, Sara Gatto

المصدر: Pediatric Reports, Vol 13, Iss 29, Pp 210-215 (2021)
Pediatric Reports

مصطلحات موضوعية: medicine.medical_specialty, endocrine system, Goiter, endocrine system diseases, medicine.medical_treatment, 030209 endocrinology & metabolism, Case Report, Thyroid function tests, Pediatrics, RJ1-570, congenital goiter, 03 medical and health sciences, 0302 clinical medicine, Thyroid dyshormonogenesis, primary congenital hypothyroidism, newborn, 030225 pediatrics, Internal medicine, medicine, biology, medicine.diagnostic_test, business.industry, Primary hypothyroidism, Pendrin, medicine.disease, thyroid dyshormonogenesis, Thyroid disorder, Endocrinology, Transgender hormone therapy, biology.protein, Medicine, Thyroglobulin, business

الوصف: Congenital goiter is an uncommon cause of neck swelling and it can be associated with hypothyroidism. We discuss a case of primary hypothyroidism with goiter presenting at birth. Ultrasound showed the enlargement of the gland and thyroid function tests detected marked hypothyroidism. Genetic analysis via next generation sequencing (NGS) was performed finding two mutations associated with thyroid dyshormonogenesis: c.7813 C > T, homozygous in the exon 45 of the thyroglobulin gene (TG) and c.1682 G > A heterozygous in exon 15 of the SLC26A4 gene (pendrin). Sanger sequencing of parents’ DNA samples revealed that the first mutation (c.7813 C > T) was inherited from both of them, while the second one (c.1682 G > A) was inherited from the mother. Hormone replacement therapy was started, following which a gradual decrease in the size of the goiter was seen with the normalization of hormonal levels. Normal infant growth status and neurological development were recorded during follow-up. Neonatal dyshormonogenetic goiter with hypothyroidism may represent an unusual cause of neonatal neck mass. Early identification and hormone replacement therapy are crucial for a better neurodevelopmental outcome. Genetic analysis is mandatory in order to reach a specific diagnosis and to elucidate new patterns of thyroid disorder.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1f833724f105c0dfa36b1817b3dc29c5Test
https://www.mdpi.com/2036-7503/13/2/29Test

المؤلفون: Merakchi, Karima, Djerbib, Sami, Soleimani, Manoocher, Dumont, Jacques-Emile, Miot, Françoise, De Deken, Xavier

المصدر: Endocrinology. 163

مصطلحات موضوعية: Grave's disease, endocrine system, endocrine system diseases, IL-4, Iodides, Hyperthyroidism, Graves Disease, Mice, Thyroxine, Endocrinology, Hypothyroidism, Sulfate Transporters, Transgenic mice, Pendrin, Animals, Interleukin-4, Iodine

الوصف: During autoimmune thyroid diseases, cytokines are known to perturb the normal function of thyrocytes. Moreover, the role of interleukine-4 (IL-4) in the pathogenesis of Graves’ disease (GD) remains controversial. In our mouse model overexpressing IL-4 in thyrocytes (Thyr-IL4), we have shown that adult mice preserved normal serum thyroxine despite an iodide uptake defect. In the present work, we evaluated if iodine restriction could uncover the thyroid deficiency in Thyr-IL4 animals as well as the role of pendrin (Pds) overexpression as a compensatory mechanism. Moreover, using an experimental model of GD we investigated the impact of a local expression of IL-4 in the incidence of hyperthyroidism. Animals of 4 weeks of age, wild-type (WT) or Thyr-IL4 carrying genetic inactivation of pendrin, were fed up for 6 weeks with a conventional or low iodine diet and analyzed for thyroid signs of hypothyroidism (circulating TSH levels, thyroid marker expression, histological alterations). Hyperthyroidism was induced in WT and Thyr-IL4 BALB/c x C57BL/6 hybrid females by repeated injections of adenovirus expressing the A-subunit of the TSH receptor (TSHR). Thyr-IL4 mice developed more rapidly elevated serum TSH under a low iodine supply with thyroid enlargement and classical histological modifications including reduction of the colloidal area. These hallmarks of hypothyroidism were all enhanced in Thyr-IL4 mice with complete pendrin invalidation. During the immunization protocol, a lower proportion of Thyr-IL4 animals developed hyperthyroidism, which was associated with a reduction of stimulating anti-TSHR antibodies. Surprisingly, thyroid immunostaining of immunized Thyr-IL4 animals revealed numerous leukocyte infiltrates relative to their WT littermates, associated with increased intrathyroidal expression of IFNg and IL-4. In conclusion, we have demonstrated that thyroid deficiency in Thyr-IL4 mice is partially compensated by the excessive iodide content of the standard chow and the overexpression of pendrin in these animals. These data further support the role of pendrin in the efflux of iodide into the follicular lumen. Furthermore, we have shown that the local expression of IL-4 in the thyroid attenuates GD progression, which was associated with enhanced thyroid infiltration by immune cells that could negatively affect thyroid function.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9da824e894e49e2da2120b2e9f548561Test
https://doi.org/10.1210/endocr/bqac107Test

المؤلفون: Mitsuo Kiriya, Yuqian Luo, Akira Kawashima, Yuta Tanimura, Hitomi Mori, Tetsuo Kondo, Koichi Suzuki

المصدر: Endocrine Journal. 68:691-699

مصطلحات موضوعية: endocrine system, medicine.medical_specialty, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Thyrotropin, Antiporters, Cell Line, chemistry.chemical_compound, Endocrinology, Thyroid-stimulating hormone, Internal medicine, medicine, Animals, Chloride-Bicarbonate Antiporters, Forskolin, biology, Chemistry, Colforsin, Thyroid, Pendrin, Apical membrane, Rats, Solute carrier family, medicine.anatomical_structure, Gene Expression Regulation, Sulfate Transporters, Thyroid Epithelial Cells, Symporter, biology.protein, Thyroid function, hormones, hormone substitutes, and hormone antagonists

الوصف: Iodine transportation is an important step in thyroid hormone biosynthesis. Uptake of iodine into the thyroid follicle is mediated mainly by the basolateral sodium-iodide symporter (NIS or solute carrier family 5 member 5: SLC5A5), and iodine efflux across the apical membrane into the follicular lumen is mediated by pendrin (SLC26A4). In addition to these transporters, SLC26A7, which has recently been identified as a causative gene for congenital hypothyroidism, was found to encode a novel apical iodine transporter in the thyroid. Although SLC5A5 and SLC26A4 have been well-characterized, little is known about SLC26A7, including its regulation by TSH, the central hormone regulator of thyroid function. Using rat thyroid FRTL-5 cells, we showed that the mRNA levels of Slc26a7 and Slc26a4, two apical iodine transporters responsible for iodine efflux, were suppressed by TSH, whereas the mRNA level of Slc5a5 was induced. Forskolin and dibutyryl cAMP (dbcAMP) had the same effect as that of TSH on the mRNA levels of these transporters. TSH, forskolin and dbcAMP also had suppressive effects on SLC26A7 promoter activity, as assessed by luciferase reporter gene assays, and protein levels, as determined by Western blot analysis. TSH, forskolin and dbcAMP also induced strong localization of Slc26a7 to the cell membrane according to immunofluorescence staining and confocal laser scanning microscopy. Together, these results suggest that TSH suppresses the expression level of Slc26a7 but induces its accumulation at the cell membrane, where it functions as an iodine transporter.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9cb9eb8e17b886c28371c2f5de6cf3e7Test
https://doi.org/10.1507/endocrj.ej20-0502Test

المؤلفون: Isabela Medeiros de Oliveira, Dalton Luiz Schiessel, Fernanda Ivanski, Viviane Matoso de Oliveira, Paula Bargi-Souza, Marco Romano, Renata Marino Romano

المصدر: Current Research in Toxicology
Current Research in Toxicology, Vol 1, Iss, Pp 124-132 (2020)

مصطلحات موضوعية: DIO1, iodothyronine deiodinase 1, PND, postnatal day, Health, Toxicology and Mutagenesis, Metabolite, Toxicology, Applied Microbiology and Biotechnology, chemistry.chemical_compound, NOAEL, no Observed Adverse Effect Level, TSH, thyrotropin, TH, thyroid hormones, TDI, tolerable daily intake, TSH, thyroid hormone receptor, TPO, thyroid peroxidase, HPT, hypothalamus-pituitary-thyroid axis, DIO3, iodothyronine deiodinase 3, Thyroid, Acrylamide, Chemistry, AA, acrylamide, BW, body weight, Allostasis, Hypothalamic–pituitary–thyroid axis, medicine.anatomical_structure, MCT-8, monocarboxylate transporter 8, Hypothalamus, Thyroid hormone metabolism, RfD, reference dose, medicine.medical_specialty, TRH, thyrotropin releasing hormone hormone, Article, DIO2, iodothyronine deiodinase 2, lcsh:RA1190-1270, Internal medicine, THRA1, thyroid hormone receptor alpha 1, medicine, EDCs, endocrine-disrupting chemicals, T4, thyroxine, Endocrine system, lcsh:Toxicology. Poisons, ComputingMethodologies_COMPUTERGRAPHICS, LDL, low lipoproteins, T3, triiodothyronine, Endocrine-disrupting chemicals, HDL, high-density lipoproteins, THRB2, thyroid hormone receptor beta 2, LOAEL, lowest Observed Adverse Effect Level, TRHR, thyrotropin releasing hormone receptor, Endocrinology, MYH6, myosin heavy chain 6, PDS, pendrin, Homeostasis, NIS, sodium/iodide symporter, Hormone

الوصف: Graphical abstract
Highlights • Acrylamide acts as endocrine disruptor for the thyroid gland function. • Acrylamide increases the transcript expression of proteins related to THs synthesis. • Exposure to acrylamide alters the hypothalamus-pituitary-thyroid axis homeostasis. • Acrylamide induces allostatic regulation of the hypothalamus-pituitary-thyroid axis.
Some endocrine-disrupting chemicals (EDCs) can affect the endocrine system through covalent interactions with specific sites, leading to deregulation of physiological homeostasis. The acrylamide (AA) present in some fried or baked foods is an example of an electrophile molecule that is able to form adducts with nucleophilic regions of nervous system proteins leading to neurological defects. A positive correlation between increased urinary AA metabolite concentration and reduced levels of thyroid hormones (TH) was described in adolescents and young adults. Thus, this study aimed to evaluate whether AA affects the physiology of the hypothalamus-pituitary-thyroid (HPT) axis and the possible repercussions in peripheral TH-target systems. For this, male Wistar rats were exposed to doses of 2.5 or 5.0 mg AA/Kg/day, based on the LOAEL (Lowest Observed Adverse Effect Level) during prepubertal development. The expression of molecular markers of HPT functionality was investigated in the hypothalamus, pituitary, thyroid, heart and liver, as well as the hormonal and lipid profiles in blood samples. Herein, we showed that AA acts as EDCs for thyroid gland function, increasing the transcript expression of several proteins related to TH synthesis and altering hypothalamus-pituitary-thyroid axis homeostasis, an effect evidenced by the higher levels of THs in the serum. Compensatory mechanisms were observed in TH-target tissues, such as an increase in Dio3 mRNA expression in the liver and a reduction in Mct8 transcript content in the hearts of AA-treated rats. Together, these results pointed out an allostatic regulation of the HPT axis induced by AA and suggest that chronic exposure to it, mainly associated with food consumption, might be related to the higher prevalence of thyroid dysfunctions.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e1ade5a1f87923921749581ed3e26df6Test
http://europepmc.org/articles/PMC8320623Test

المؤلفون: Eleftheriadou, Anna-Maria

مصطلحات موضوعية: endocrine system, pendrin, autoantibodies, food and beverages, NIS, health care economics and organizations, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit

الوصف: Introduction: Iodine is an essential component in thyroid hormone biosynthesis. Iodide transport through thyrocytes is mainly mediated by the basolateral sodium-iodide-symporter (NIS, SLC5A5) and the apical anion exchanger pendrin (PDS, SLC26A4). The role of TPO- and TSH-receptor-autoantibodies in the pathogenesis and diagnosis of autoimmune thyroid disease is well established. However, reports regarding the prevalence and diagnostic utility of autoantibodies (aAb) against NIS and PDS have been contradictory, possibly due to small study groups and underlying methodological differences of the published papers. Methods: We established two novel non-radioactive assays using the full length antigens NIS und PDS. For this purpose, NIS and PDS were recombinantly expressed as fusion protein with firefly-luciferase in stably transfected HEK293 cells. Serum samples from a large cohort of 323 thyroid patients and 400 healthy controls were screened for NIS- and PDS-aAb. Results: Thyroid patients showed an approximately fourfold higher prevalence of NIS-aAb (7.7%) than controls (1.8%), while the prevalence of PDS-aAb was similar in thyroid patients and controls (7.7% vs. 5.0%). The highest prevalence of NIS- and PDS-aAb was seen in the subgroup of Graves��� disease patients (12.3% and 11.0%, respectively). No correlation was found between the investigated aAb-titers and TPO-aAb or TSH-receptor-aAb or selenium or zinc status. The reproducibility of assay signals was verified with respect to linearity, stability and absence of matrix effects. Conclusions: The results are in agreement with recent studies. While a determination of PDS-aAb in thyroid patients does not yet seem to be of diagnostic value, a possible relevance of NIS-aAb for an improved diagnosis of thyroid disease was shown.
Einleitung: Iod ist ein essentieller Bestandteil in der Schilddr��senhormon-Biosynthese. Der Iodid-Transport durch die Thyreozyten erfolgt haupts��chlich durch den basolateralen Natrium-Iodid-Symporter (NIS, SLC5A5) und den apikalen Anionen-Austauscher Pendrin (PDS, SLC26A4). Die Rolle von TPO- und TSH Rezeptor-Autoantik��rpern in der Pathogenese und Diagnostik von autoimmunbedingten Schilddr��senerkrankungen ist gut etabliert. Widerspr��chlich zeigen sich allerdings Berichte ��ber die Pr��valenz und den diagnostischen Nutzen von Autoantik��rpern (aAk) gegen NIS und PDS; dies ist m��glicherweise auf die kleinen Studiengruppen und methodische Unterschiede der publizierten Arbeiten zur��ckzuf��hren. Methoden: Es erfolgte die Etablierung zweier neuartiger nicht-radioaktiver Assays mit den Antigenen NIS und PDS in voller L��nge. Daf��r wurden NIS und PDS rekombinant als Fusionsprotein mit Firefly-Luciferase in stabil transfizierten HEK293-Zellen exprimiert. Hiermit wurden Serumproben einer gro��en Kohorte von 323 Schilddr��senpatienten und 400 gesunden Kontrollen vermessen. Ergebnisse: Schilddr��senpatienten zeigten eine ca. viermal h��here Pr��valenz f��r NIS-aAk (7,7 %) als Kontrollen (1,8 %), w��hrend die Pr��valenz von PDS-aAk bei Schilddr��senpatienten und Kontrollen ��hnlich war (7,7 % vs. 5,0 %). Die h��chste Pr��valenz von NIS- und PDS-aAk zeigte sich in der Subgruppe der M. Basedow Patienten (12,3 % und 11,0 %). Es zeigte sich keine Beziehung der untersuchten aAk zu den TPO aAk oder TSH-Rezeptor-aAk-Titern bzw. dem Selen- oder Zinkstatus. Die Reproduzierbarkeit der Assaysignale wurde hinsichtlich Linearit��t, Stabilit��t und Abwesenheit von Matrixeffekten verifiziert. Schlussfolgerungen: Die Ergebnisse stehen in ��bereinstimmung mit aktuellen Studien. W��hrend der Bestimmung von PDS-aAk bei Schilddr��senpatienten derzeit kein diagnostischer Wert zukommt, zeigte sich eine m��gliche Relevanz von NIS-aAk f��r eine verbesserte Diagnostik von Schilddr��senerkrankungen.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::166425ffe15b2650feea9a7e25dc2b0dTest

المؤلفون: Miguel Campos, Martina Dettwiler, Simon Leonhard April-Monn, Jana Jankovic, Martin Kessler, Kerstin Hahn, Sven Rottenberg, Eve Tièche, Matthias S. Dettmer, Martin González Fernández

المصدر: Veterinary pathology. 58(6)

مصطلحات موضوعية: Sodium-iodide symporter, endocrine system, endocrine system diseases, General Veterinary, biology, Chemistry, Thyroid, Pendrin, medicine.disease, Follicular cell, Immunohistochemistry, Thyroid carcinoma, Organoids, medicine.anatomical_structure, Dogs, Thyroid peroxidase, biology.protein, Cancer research, medicine, Animals, Dog Diseases, Thyroid Neoplasms, Thyroid cancer, Iodine

الوصف: 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.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::03f5cdc1bdf3987ac31c900e9958d423Test
https://pubmed.ncbi.nlm.nih.gov/34056980Test

المؤلفون: Mahmood Y. Bilal, Svetlana Dambaeva, Joanne Kwak-Kim, Alice Gilman-Sachs, Kenneth D. Beaman

المصدر: Frontiers in Immunology
Frontiers in Immunology, Vol 8 (2017)

مصطلحات موضوعية: lcsh:Immunologic diseases. Allergy, 0301 basic medicine, nutritional immunology, medicine.medical_specialty, Chemokine, endocrine system, pendrin, medicine.medical_treatment, Immunology, thyroglobulin, Jurkat cells, 03 medical and health sciences, Immune system, Thyroid peroxidase, Internal medicine, medicine, Immunology and Allergy, Original Research, iodine deficiency, thyroid hormones, Triiodothyronine, biology, iodine, Thyroid, Pendrin, NIS, RNAseq, Molecular biology, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, biology.protein, Thyroglobulin, lcsh:RC581-607

الوصف: Iodine is an essential element required for the function of all organ systems. Although the importance of iodine in thyroid hormone synthesis and reproduction is well known, its direct effects on the immune system are elusive. Human leukocytes expressed mRNA of iodide transporters (NIS and PENDRIN) and thyroid-related proteins [thyroglobulin (TG) and thyroid peroxidase (TPO)]. The mRNA levels of PENDRIN and TPO were increased whereas TG transcripts were decreased post leukocyte activation. Flow cytometric analysis revealed that both PENDRIN and NIS were expressed on the surface of leukocyte subsets with the highest expression occurring on monocytes and granulocytes. Treatment of leukocytes with sodium iodide (NaI) resulted in significant changes in immunity-related transcriptome with an emphasis on increased chemokine expression as probed with targeted RNASeq. Similarly, treatment of leukocytes with NaI or Lugol’s iodine induced increased protein production of both pro- and anti-inflammatory cytokines. These alterations were not attributed to iodide-induced de novo thyroid hormone synthesis. However, upon incubation with thyroid-derived TG, primary human leukocytes but not Jurkat T cells released thyroxine and triiodothyronine indicating that immune cells could potentially influence thyroid hormone balance. Overall, our studies reveal the novel network between human immune cells and thyroid-related molecules and highlight the importance of iodine in regulating the function of human immune cells.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::905c53b6dd04f52524fb874b72e4bfd2Test
https://pubmed.ncbi.nlm.nih.gov/29187856Test

المؤلفون: Takuya Yazawa, Toru Kimura, Shinji Saitoh, Haruo Mizuno, Tatsushi Tanaka, Michihiro Tateyama, Hiroshi Kamma, Jun Ishii, Atsushi Suzuki, Kohei Aoyama, Yu Arimasu, I-Shan Chen, Yoshihiro Kubo

المصدر: Communications Biology
Communications Biology, Vol 2, Iss 1, Pp 1-11 (2019)

مصطلحات موضوعية: Male, Thyroid Hormones, Cell biology, endocrine system, medicine.medical_specialty, endocrine system diseases, Iodide, Nonsense mutation, Thyroid Gland, Medicine (miscellaneous), Pathogenesis, Antiporters, Article, General Biochemistry, Genetics and Molecular Biology, Cell Line, Dogs, Endocrinology, Internal medicine, Congenital Hypothyroidism, Genetics, medicine, Animals, Humans, Iodide transport, lcsh:QH301-705.5, Pendred syndrome, chemistry.chemical_classification, biology, Goiter, business.industry, Thyroid, Infant, Newborn, Haplorhini, Pendrin, medicine.disease, Congenital hypothyroidism, medicine.anatomical_structure, lcsh:Biology (General), chemistry, Codon, Nonsense, Sulfate Transporters, Child, Preschool, biology.protein, Female, General Agricultural and Biological Sciences, business, Hormone

الوصف: Iodide transport and storage in the thyroid follicles is crucial for thyroid hormone synthesis. Pendrin, the iodide exporter that transports iodide to thyroid follicles, is responsible for Pendred syndrome, a disorder characterized by congenital hypothyroidism and hearing loss. However, thyroid hormone levels are basically normal in patients with Pendred syndrome, indicating the presence of another unknown iodide transporter. Here, we show that SLC26A7 is a novel iodide transporter in the thyroid. We observe that SLC26A7 is specifically expressed in normal thyroid tissues and demonstrate its function in iodide transport. Using whole-exome sequencing, we also find a homozygous nonsense mutation in SLC26A7 (c.1498 C > T; p.Gln500Ter) in two siblings with congenital goitrous hypothyroidism. The mutated SLC26A7 protein shows an abnormal cytoplasmic localisation and lacks the iodide transport function. These results reveal that SLC26A7 functions as a novel iodide transporter in the thyroid and its dysfunction affects thyroid hormonogenesis in humans and causes congenital goitrous hypothyroidism.
Jun Ishii and Atsushi Suzuki et al. report the identification of SLC26A7 as a novel iodide transporter expressed in the thyroid. They identify a nonsense mutation in SLC26A7 in siblings with congenital hypothyroidism and goitre using whole-exome sequencing, implicating this transporter in disease.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b5bd42384dbad88dc2dc84d212e6072dTest
https://doi.org/10.1038/s42003-019-0503-6Test

المؤلفون: Jin-Wei Zhang, Xiao-Yi Chen, Chu-Hui Lin, Wen-Wei Zheng, Wang-Gen Li, Wang Xiang, Yi-Xiong Lei, Jia-Luan Huang, Jiang Qian, Li-Hua Yang

المصدر: Biological Trace Element Research. 172:193-200

مصطلحات موضوعية: 0301 basic medicine, Sodium-iodide symporter, endocrine system, medicine.medical_specialty, Goiter, Endocrinology, Diabetes and Metabolism, Anion Transport Proteins, Clinical Biochemistry, Iodide, Thyroid Gland, chemistry.chemical_element, Iodine, Biochemistry, Inorganic Chemistry, Mice, 03 medical and health sciences, Internal medicine, medicine, Animals, Colloids, chemistry.chemical_classification, Mice, Inbred BALB C, Symporters, biology, Chemistry, Biochemistry (medical), Thyroid, General Medicine, Pendrin, Iodides, medicine.disease, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Sulfate Transporters, Symporter, biology.protein, Female, Thyroid function

الوصف: It is well known that excess iodide can lead to thyroid colloid retention, a classic characteristic of iodide-induced goiter. However, the mechanism has not been fully unrevealed. Iodide plays an important role in thyroid function at multiple steps of thyroid colloid synthesis and transport among which sodium/iodide symporter (NIS) and pendrin are essential. In our study, we fed female BALB/c mice with different concentrations of high-iodine water including group A (control group, 0 μg/L), group B (1500 μg/L), group C (3000 μg/L), group D (6000 μg/L), and group E (12,000 μg/L). After 7 months of feeding, we found that excess iodide could lead to different degrees of thyroid colloid retention. Besides, NIS and pendrin expression were downregulated in the highest dose group. The thyroid iodide intake function detected by urine iodine assay and thyroidal (125)I experiments showed that the urine level of iodine increased, while the iodine intake rate decreased when the concentration of iodide used in feeding water increased (all p

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f0d466971378a28a5b2c65880044f9e2Test
https://doi.org/10.1007/s12011-015-0580-4Test