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Even so, the regulation of gene\/protein expression in the hypothalamus, pituitary and thyroid by chronic perchlorate exposure was not completely elucidated. Therefore, this study aimed to investigate the underlying mechanisms involved in the disruption of hypothalamus\u2010pituitary\u2010thyroid axis by chronic perchlorate exposure. Male Wistar rats were treated or not with NaClO<jats:sub>4<\/jats:sub>in the drinking water (35 mg\/Kg\/day) for 60 days. Thereafter, hormone\/cytokines serum levels were measured through multiplex assays; genes\/proteins expression were investigated by qPCR\/Western Blotting and thyroid morphology was evaluated through histological analysis. Serum TSH levels were increased and serum T<jats:sub>4<\/jats:sub>\/T<jats:sub>3<\/jats:sub>levels were decreased in perchlorate\u2010treated animals. This treatment also altered the thyrotropin\u2010releasing hormone mRNA\/protein content in the hypothalamus. Additionally, the expression of both subunits of TSH were increased in the pituitary of perchlorate\u2010treated rats, which also presented significant alterations in the thyroid morphology\/gene expression. Furthermore, perchlorate exposure reduced liver<jats:italic>Dio1<\/jats:italic>mRNA expression and increased the content of pro\u2010inflammatory cytokines in the thyroid and the serum. In conclusion, our study adds novel findings about the perchlorate\u2010induced disruption of the hypothalamus\u2010pituitary\u2010thyroid axis gene\/protein expression in male rats. The data presented herein also suggest that perchlorate induces thyroid and systemic inflammation through the increased production of cytokines. Taken together, our results suggest that perchlorate contamination should be monitored, especially in the individuals most susceptible to the deleterious effects of reduced levels of thyroid hormones.<\/jats:p>","DOI":"10.1002\/tox.22509","type":"journal-article","created":{"date-parts":[[2017,11,15]],"date-time":"2017-11-15T07:22:39Z","timestamp":1510730559000},"page":"209-219","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Evaluation of hypothalamus\u2010pituitary\u2010thyroid axis function by chronic perchlorate exposure in male rats"],"prefix":"10.1002","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9146-6583","authenticated-orcid":false,"given":"Caroline","family":"Serrano\u2010Nascimento","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics Institute of Biomedical Sciences, University of S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamile","family":"Calil\u2010Silveira","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Institute of Biomedical Sciences, University of S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Dalbosco","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology Institute of Biomedical Sciences, University of S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Telma Tenorio","family":"Zorn","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology Institute of Biomedical Sciences, University of S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Tereza","family":"Nunes","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Institute of Biomedical Sciences, University of S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,11,15]]},"reference":[{"issue":"1","key":"e_1_2_6_2_1","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0031-6997(24)01350-4","article-title":"Perchlorate and the thyroid gland","volume":"50","author":"Wolff J.","year":"1998","journal-title":"Pharmacol Rev."},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/MED.0000000000000090"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2009.08.009"},{"issue":"4","key":"e_1_2_6_5_1","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/sj.jes.7500535","article-title":"Perchlorate exposure of the US Population, 2001\u20132002","volume":"17","author":"Blount BC","year":"2007","journal-title":"J Expo Sci Environ Epidemiol."},{"issue":"21","key":"e_1_2_6_6_1","doi-asserted-by":"crossref","first-page":"6608","DOI":"10.1021\/es061321z","article-title":"Perchlorate in the United States. 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