2004 Fiscal Year Final Research Report Summary
Adverse effects of endocrine-disrupting chemicals and the mechanism via nuclear receptor in relation to the risk assessment
| Project/Area Number |
14370121
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hygiene
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| Research Institution | Nagoya University |
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Principal Investigator |
NASU Tamie Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (10020794)
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| Co-Investigator(Kenkyū-buntansha) |
ICHIHARA Gaku Nagoya University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (90252238)
AOYAMA Toshifumi Shinshu University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (50231105)
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| Project Period (FY) |
2002 – 2004
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| Keywords | PPARalpha / AhR / 2,4-dichlorophenoxyacetic acid / pentachlorophenol / thyroid hormone / reproductive toxicity / testosterone / knockout mice |
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| Research Abstract |
2,4-Dichlorophenoxyacetic Acid(2,4-D) clearly decreased serum and testicular testosterone level、and caused damage of seminiferous tubules and vacuolar of Sertoli cells in the wild-type mice. These changes could not be observed in peroxisome proliferators-activated receptor α(PPAR α)-null mice, suggesting that 2,4-D-induced toxic effects are related to PPAR α. We also investigated the effects of 2,4-D on the expression of protein involved in cholesterol de novo synthesis and testosterone synthesis in Leydig cells. 2,4-D treatment slightly influenced the expression of proteins involved in testosterone synthesis, but clearly decreased cholesterol level and also the expression ofenzymes involved in cholesterol de novo synthesis. These results suggest that decreased in testosterone by 2,4-D treatment may result in the histopathological change of semoiniferous epithelium and Sertoli cells.
The effects of pentachlorophenol(PCP) on thyroid hormone (T4) using male wild-type and aromatic hydrocarbon receptor(AhR)-null mice. PCP increase AhR-mRNA in the wild-type mice, but not in AhR-null mice, suggesting a ligand of PCP for AhR. PCP treatment increased UDP-glucuronosyltransferase(UGT) 1A1-mRNA and UGT1A6-mRNA. PCP treatment also increased the metabolic rate of 1-naphtol as a substrate for UGT1A6, but did not affect that of bilirubin as a substrate of UGT1A1 in the wild-type mice. In the AhR-null mice, however, these changes observed in the wild-type mice could not be observed. These results indicate that PCP induces UGT1A6 via AhR. PCP treatment decreased T4 level in either wild-type mice or AhR-null mice, suggesting that decrease in T4 level by PCP treatment is not dependent on AhR.
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Research Products
(22 results)
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[Book] 分子予防環境医学2003
Author(s)
那須民江(分担)
Total Pages
768
Publisher
本の泉社
Description
「研究成果報告書概要(和文)」より
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