TRIAC disrupts cerebral thyroid hormone action via negative feedback and heterogenous distribution among organs
Summary: As 3,3′,5-triiodothyroacetic acid (TRIAC), a metabolite of thyroid hormones (THs), was previously detected in sewage effluent, we aimed to investigate exogenous TRIAC’s potential for endocrine disruption. We administered either TRIAC or 3,3′,5-triiodo-L-thyronine (LT3) to euthyroid mice and...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-07-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223012129 |
| _version_ | 1797774562249670656 |
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| author | Ichiro Yamauchi Takuro Hakata Yohei Ueda Taku Sugawa Ryo Omagari Yasuo Teramoto Shoji F. Nakayama Daisuke Nakajima Takuya Kubo Nobuya Inagaki |
| author_facet | Ichiro Yamauchi Takuro Hakata Yohei Ueda Taku Sugawa Ryo Omagari Yasuo Teramoto Shoji F. Nakayama Daisuke Nakajima Takuya Kubo Nobuya Inagaki |
| author_sort | Ichiro Yamauchi |
| collection | DOAJ |
| description | Summary: As 3,3′,5-triiodothyroacetic acid (TRIAC), a metabolite of thyroid hormones (THs), was previously detected in sewage effluent, we aimed to investigate exogenous TRIAC’s potential for endocrine disruption. We administered either TRIAC or 3,3′,5-triiodo-L-thyronine (LT3) to euthyroid mice and 6-propyl-2-thiouracil-induced hypothyroid mice. In hypothyroid mice, TRIAC administration suppressed the hypothalamus-pituitary-thyroid (HPT) axis and upregulated TH-responsive genes in the pituitary gland, the liver, and the heart. We observed that, unlike LT3, TRIAC administration did not upregulate cerebral TH-responsive genes. Measurement of TRIAC contents suggested that TRIAC was not efficiently trafficked into the cerebrum. By analyzing euthyroid mice, we found that cerebral TRIAC content did not increase despite TRIAC administration at higher concentrations, whereas serum levels and cerebral contents of THs were substantially decreased. Disruption by TRIAC is due to the additive effects of circulating endogenous THs being depleted via a negative feedback loop involving the HPT axis and heterogeneous distribution of TRIAC among different organs. |
| first_indexed | 2024-03-12T22:22:52Z |
| format | Article |
| id | doaj.art-98d3586dcee3471484aa21791263dc6b |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-12T22:22:52Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-98d3586dcee3471484aa21791263dc6b2023-07-23T04:55:40ZengElsevieriScience2589-00422023-07-01267107135TRIAC disrupts cerebral thyroid hormone action via negative feedback and heterogenous distribution among organsIchiro Yamauchi0Takuro Hakata1Yohei Ueda2Taku Sugawa3Ryo Omagari4Yasuo Teramoto5Shoji F. Nakayama6Daisuke Nakajima7Takuya Kubo8Nobuya Inagaki9Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan; Corresponding authorDepartment of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, JapanDepartment of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, JapanDepartment of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, JapanHealth and Environmental Risk Division, National Institute for Environmental Studies, Tsukuba, Ibaraki 305-8506, JapanHealth and Environmental Risk Division, National Institute for Environmental Studies, Tsukuba, Ibaraki 305-8506, JapanHealth and Environmental Risk Division, National Institute for Environmental Studies, Tsukuba, Ibaraki 305-8506, JapanHealth and Environmental Risk Division, National Institute for Environmental Studies, Tsukuba, Ibaraki 305-8506, Japan; Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, JapanDepartment of Material Chemistry, Graduate School of Engineering, Kyoto University, Nishikyo-ku, Kyoto 615-8530, JapanDepartment of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan; Medical Research Institute KITANO HOSPITAL, PIIF Tazuke-kofukai, Osaka 530-8480, JapanSummary: As 3,3′,5-triiodothyroacetic acid (TRIAC), a metabolite of thyroid hormones (THs), was previously detected in sewage effluent, we aimed to investigate exogenous TRIAC’s potential for endocrine disruption. We administered either TRIAC or 3,3′,5-triiodo-L-thyronine (LT3) to euthyroid mice and 6-propyl-2-thiouracil-induced hypothyroid mice. In hypothyroid mice, TRIAC administration suppressed the hypothalamus-pituitary-thyroid (HPT) axis and upregulated TH-responsive genes in the pituitary gland, the liver, and the heart. We observed that, unlike LT3, TRIAC administration did not upregulate cerebral TH-responsive genes. Measurement of TRIAC contents suggested that TRIAC was not efficiently trafficked into the cerebrum. By analyzing euthyroid mice, we found that cerebral TRIAC content did not increase despite TRIAC administration at higher concentrations, whereas serum levels and cerebral contents of THs were substantially decreased. Disruption by TRIAC is due to the additive effects of circulating endogenous THs being depleted via a negative feedback loop involving the HPT axis and heterogeneous distribution of TRIAC among different organs.http://www.sciencedirect.com/science/article/pii/S2589004223012129Chemical substanceEndocrine disrupterBiochemistryEndocrine system physiology |
| spellingShingle | Ichiro Yamauchi Takuro Hakata Yohei Ueda Taku Sugawa Ryo Omagari Yasuo Teramoto Shoji F. Nakayama Daisuke Nakajima Takuya Kubo Nobuya Inagaki TRIAC disrupts cerebral thyroid hormone action via negative feedback and heterogenous distribution among organs iScience Chemical substance Endocrine disrupter Biochemistry Endocrine system physiology |
| title | TRIAC disrupts cerebral thyroid hormone action via negative feedback and heterogenous distribution among organs |
| title_full | TRIAC disrupts cerebral thyroid hormone action via negative feedback and heterogenous distribution among organs |
| title_fullStr | TRIAC disrupts cerebral thyroid hormone action via negative feedback and heterogenous distribution among organs |
| title_full_unstemmed | TRIAC disrupts cerebral thyroid hormone action via negative feedback and heterogenous distribution among organs |
| title_short | TRIAC disrupts cerebral thyroid hormone action via negative feedback and heterogenous distribution among organs |
| title_sort | triac disrupts cerebral thyroid hormone action via negative feedback and heterogenous distribution among organs |
| topic | Chemical substance Endocrine disrupter Biochemistry Endocrine system physiology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223012129 |
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