{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:32:30Z","timestamp":1791379950245,"version":"4.3.3"},"reference-count":41,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T00:00:00Z","timestamp":1649376000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","award":["H30\u2010Kagaku\u2010Shitei\u2010003"],"award-info":[{"award-number":["H30\u2010Kagaku\u2010Shitei\u2010003"]}],"id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Although measurements of blood hormone levels in rodent toxicological studies can provide important information on the mechanisms of toxicity and extrapolation to humans, there are several difficulties such as large individual differences and limited sample volume. To develop a more simplified method that does not depend solely on blood samples, we examined the possible application of immunohistochemistry for detecting endocrine disruptors in short\u2010term studies. Aminotriazole (AMT), propylthiouracil (PTU), phenobarbital, aminoglutethimide (AGT), estradiol, and vitamin D3 were administered orally to 6\u2010week\u2010old male and female SD rats (five\/group) for 28\u2009days. Measurements of serum hormone levels revealed decreases in triiodothyronine (T3) and thyroxine (T4) in the AMT and PTU groups, an increase in thyroid stimulating hormone (TSH) in the AMT, PTU, and AGT groups, and an increase in adrenocorticotrophic hormone in the AGT group. Increased thyroid, pituitary, and adrenal gland weights; histopathological lesions, including follicular hypertrophy\/hyperplasia, hypertrophy\/vacuolation of anterior pituitary cells, and increased adrenocortical vacuolation were observed in association with the hormone level changes. Immunohistochemical analysis revealed a decreased T4 level in the thyroid gland of the AMT and PTU groups and an increased area of TSH positive immunostaining in the pituitary gland of the AMT, PTU, and AGT groups, consistent with the changes in serum T4 and TSH levels, respectively. These results suggest that histopathological analysis and immunohistochemistry for T4 and TSH might be useful and sensitive methods of detecting thyroid dysfunction, and that combining organ weight measurements is a reliable parameter of detecting endocrine disruptors.<\/jats:p>","DOI":"10.1002\/jat.4327","type":"journal-article","created":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T09:16:44Z","timestamp":1649236604000},"page":"1603-1617","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Histopathological and immunohistochemical evaluation for detecting changes in blood hormone levels caused by endocrine disruptors in a 28\u2010day repeated\u2010dose study in rats"],"prefix":"10.1002","volume":"42","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"}]},{"given":"Yasuko","family":"Mizuta","sequence":"additional","affiliation":[{"name":"Division of Pathology National Institute of Health Sciences  Kawasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young\u2010Man","family":"Cho","sequence":"additional","affiliation":[{"name":"Division of Pathology National Institute of Health Sciences  Kawasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Ide","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  Joso Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Tajima","sequence":"additional","affiliation":[{"name":"Toxicology Division Institute of Environmental Toxicology  Joso Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Aoyama","sequence":"additional","affiliation":[{"name":"Toxicology Division Institute of Environmental Toxicology  Joso 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":[[2022,4,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/0192623312466959"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1006\/toxs.1998.2469"},{"issue":"1","key":"e_1_2_8_4_1","first-page":"76","article-title":"Metabolism of estradiol, ethynylestradiol, and moxestrol in rat uterus, vagina, and aorta: Influence of sex steroid treatment","volume":"29","author":"Blom M. 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