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To develop more efficient methods for detecting thyroid disruptors, we compared histopathological and immunohistochemical findings in the thyroid and pituitary glands with blood hormone levels. Six\u2010week\u2010old male and female Sprague\u2013Dawley rats (five rats per group) were treated with multiple doses of the thyroid peroxidase inhibitors propylthiouracil (PTU) and methimazole by gavage for 28\u2009days. Significant decreases in serum T3 and T4 and increases in TSH were observed in the \u22651\u00a0mg\/kg PTU and \u22653\u00a0mg\/kg methimazole groups. An increase in TSH was also detected in male rats in the 0.3\u00a0mg\/kg PTU group. Histopathological and immunohistochemical analyses revealed that follicular cell hypertrophy and decreased T4 and T3 expressions in the thyroid gland were induced at doses lower than doses at which significant changes in serum hormone levels were observed, suggesting that these findings may be more sensitive than blood hormone levels. Significant increases in thyroid weights, Ki67\u2010positive thyroid follicular cell counts, and TSH\u2010positive areas in the pituitary gland were detected at doses comparable with those at which changes in serum T4 and TSH levels were observed, indicating that these parameters may also be useful for evaluation of antithyroid effects. Combining these parameters may be effective for detecting antithyroid substances without relying on hormone measurements.<\/jats:p>","DOI":"10.1002\/jat.4604","type":"journal-article","created":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T10:06:32Z","timestamp":1712052392000},"page":"1084-1103","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Comparison of the sensitivity of histopathological and immunohistochemical analyses and blood hormone levels for early detection of antithyroid effects in rats treated with thyroid peroxidase inhibitors"],"prefix":"10.1002","volume":"44","author":[{"given":"Hirotoshi","family":"Akane","sequence":"first","affiliation":[{"name":"Division of Pathology National Institute of Health Sciences  Kawasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1646-4603","authenticated-orcid":false,"given":"Takeshi","family":"Toyoda","sequence":"additional","affiliation":[{"name":"Division of Pathology National Institute of Health Sciences  Kawasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4184-0367","authenticated-orcid":false,"given":"Kohei","family":"Matsushita","sequence":"additional","affiliation":[{"name":"Division of Pathology National Institute of Health Sciences  Kawasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomomi","family":"Morikawa","sequence":"additional","affiliation":[{"name":"Division of Pathology National Institute of Health Sciences  Kawasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Kosaka","sequence":"additional","affiliation":[{"name":"Toxicology Division Institute of Environmental Toxicology  Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Tajima","sequence":"additional","affiliation":[{"name":"Toxicology Division Institute of Environmental Toxicology  Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Aoyama","sequence":"additional","affiliation":[{"name":"Toxicology Division Institute of Environmental Toxicology  Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4454-3838","authenticated-orcid":false,"given":"Kumiko","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Division of Pathology National Institute of Health Sciences  Kawasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.4327"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/0192623312466959"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI60047"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18122583"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/019262301301418829"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/09513590701267651"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-020-02961-6"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfac038"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7827-8-14"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfz227"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yhbeh.2011.06.003"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/50.1.45"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.992883"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI94417"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/0192623315579943"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/edrv.22.5.0444"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2009-0041"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2019.04.010"},{"issue":"4","key":"e_1_2_8_20_1","first-page":"865","article-title":"Effects of diethylstilbestrol and propylthiouracil on the rat pituitary. 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