{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T04:19:58Z","timestamp":1781842798581,"version":"3.54.5"},"reference-count":49,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,12,19]],"date-time":"2017-12-19T00:00:00Z","timestamp":1513641600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004586","name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004586","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Na<jats:sup>+<\/jats:sup>\/I<jats:sup>\u2212<\/jats:sup> symporter (<jats:styled-content style=\"fixed-case\">NIS<\/jats:styled-content>) transports iodide into thyrocytes, a fundamental step for thyroid hormone biosynthesis. Our aim was to evaluate <jats:styled-content style=\"fixed-case\">NIS<\/jats:styled-content> regulation in different status of goitrogenesis and its underlying mechanisms. Wistar rats were treated with methimazole (<jats:styled-content style=\"fixed-case\">MMI<\/jats:styled-content>) for 5 and 21\u00a0days, to achieve different status of goiter. We then evaluated the effect of <jats:styled-content style=\"fixed-case\">MMI<\/jats:styled-content> removal for 1\u00a0day (R1d), after 5 (R1d\u20105d) or 21 (R1d\u201021d) days of <jats:styled-content style=\"fixed-case\">MMI<\/jats:styled-content> treatment. <jats:styled-content style=\"fixed-case\">MMI<\/jats:styled-content> increased thyroid weight, iodide uptake and in vitro <jats:styled-content style=\"fixed-case\">TPO<\/jats:styled-content> activity in a time\u2010dependent way. Although <jats:styled-content style=\"fixed-case\">MMI<\/jats:styled-content> removal evoked a rapid normalization of <jats:styled-content style=\"fixed-case\">TPO<\/jats:styled-content> activity in R1d\u20105d, it was still high in R1d\u201021d. On the other hand, iodide uptake was rapidly down\u2010regulated in R1d\u201021d, but not in R1d\u20105d, suggesting that the increased <jats:styled-content style=\"fixed-case\">TPO<\/jats:styled-content> activity in R1d\u201021d led to increased intraglandular organified iodine (I\u2010X), which is known to inhibit iodide uptake. Since <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u03b2 has been shown to mediate some effects of I\u2010X, we evaluated <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u03b2 and <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u03b2 receptor <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> levels, which were increased in R1d\u201021d. Moreover, it has been demonstrated that <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u03b2 stimulates <jats:styled-content style=\"fixed-case\">NOX<\/jats:styled-content>4. Accordingly, our data revealed increased <jats:styled-content style=\"fixed-case\">NOX<\/jats:styled-content>4 expression and H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> generation in R1d\u201021d. Finally, we evaluated the effect of H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> on <jats:styled-content style=\"fixed-case\">NIS<\/jats:styled-content> function and <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> levels in <jats:styled-content style=\"fixed-case\">PCCL<\/jats:styled-content>3 thyroid cell line, which were reduced. Thus, the present study suggests that there is a relationship between the size of the goiter and <jats:styled-content style=\"fixed-case\">NIS<\/jats:styled-content> regulation and that the mechanism might involve I\u2010X, <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u03b2, <jats:styled-content style=\"fixed-case\">NOX<\/jats:styled-content>4 and increased <jats:styled-content style=\"fixed-case\">ROS<\/jats:styled-content> production.<\/jats:p>","DOI":"10.1111\/1440-1681.12887","type":"journal-article","created":{"date-parts":[[2017,11,7]],"date-time":"2017-11-07T17:52:38Z","timestamp":1510077158000},"page":"326-334","source":"Crossref","is-referenced-by-count":13,"title":["Regulation of thyroid sodium\u2010iodide symporter in different stages of goiter: Possible involvement of reactive oxygen species"],"prefix":"10.1111","volume":"45","author":[{"given":"L\u00edvia P L","family":"Matos","sequence":"first","affiliation":[{"name":"Departamento de Ci\u00eancias B\u00e1sicas ISNF Universidade Federal Fluminense  Nova Friburgo RJ Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo Cortez Cardoso","family":"Penha","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Fisiologia End\u00f3crina Doris Rosenthal IBCCF Universidade Federal do Rio de Janeiro  Rio de Janeiro RJ Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciene C","family":"Cardoso\u2010Weide","sequence":"additional","affiliation":[{"name":"Departamento de Patologia Faculdade de Medicina Universidade Federal Fluminense  Niteroi RJ Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana L","family":"Freitas","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Fisiologia End\u00f3crina Doris Rosenthal IBCCF Universidade Federal do Rio de Janeiro  Rio de Janeiro RJ Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diorney L S G","family":"Silva","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Fisiologia End\u00f3crina Doris Rosenthal IBCCF Universidade Federal do Rio de Janeiro  Rio de Janeiro RJ Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7300-2718","authenticated-orcid":false,"given":"Andrea C F","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Fisiologia End\u00f3crina Doris Rosenthal IBCCF Universidade Federal do Rio de Janeiro  Rio de Janeiro RJ Brazil"},{"name":"Campus Duque de Caxias NUMPEX\u2010Bio Universidade Federal do Rio de Janeiro  Duque de Caxias RJ Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,12,19]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp0801880"},{"key":"e_1_2_7_3_1","first-page":"1115","article-title":"Serum TSH, thyroglobulin, and thyroidal disorders in 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