TRIAC disrupts cerebral thyroid hormone action via negative feedback and heterogenous distribution among organs
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- Yamauchi, Ichiro
- Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University
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- Hakata, Takuro
- Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University
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- Ueda, Yohei
- Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University
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- Sugawa, Taku
- Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University
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- Omagari, Ryo
- Health and Environmental Risk Division, National Institute for Environmental Studies
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- Teramoto, Yasuo
- Health and Environmental Risk Division, National Institute for Environmental Studies
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- Nakayama, Shoji F.
- Health and Environmental Risk Division, National Institute for Environmental Studies
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- Nakajima, Daisuke
- Health and Environmental Risk Division, National Institute for Environmental Studies; Graduate School of Pharmaceutical Sciences, Chiba University
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- Kubo, Takuya
- Department of Material Chemistry, Graduate School of Engineering, Kyoto University
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- Inagaki, Nobuya
- Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University; Medical Research Institute KITANO HOSPITAL, PIIF Tazuke-kofukai
Abstract
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.
Journal
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- iScience
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iScience 26 (7), 2023-07-21
Elsevier BV
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Details 詳細情報について
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- CRID
- 1050296808060796032
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- ISSN
- 25890042
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- HANDLE
- 2433/284042
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- Text Lang
- en
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- Article Type
- journal article
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- Data Source
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- IRDB