Effects of Environmental Antiandrogenic Chemicals on Expression of Androgen-Responsive Genes in Rat Prostate Lobes
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概要
- 論文の詳細を見る
Rat prostate, which is usually used in the Hershberger assay for evaluating the antiandrogenic activity of environmental chemicals in vivo, has a complex structure consisting 4 lobes, i.e., the ventral prostate (VP), lateral prostate (LP), dorsal prostate (DP) and anterior prostate (AP). The VP is considered to have no counterpart in primates, while the LP and DP are histologically similar to human prostate. However, the Hershberger assay focuses on the VP, not the other lobes. Moreover, there are few other methods for assessment of antiandrogenic activity in vivo. We therefore investigated androgen-responsive genes in the DP, as well as VP, following treatment with environmental chemicals reported to be androgen antagonists. Male castrated F344 rats were treated with testosterone (0.5mg・kg^<-1>・day^<-1>) alone or together with flutamide (6mg・kg^<-1>・day^<-1>) as a reference antiandrogen or fenthion (25mg・kg^<-1>・day^<-1>) or fenitrothion (25mg・kg^<-1>・day^<-1>) or 2,4,4′-trihydroxybenzophenone (2,4,4′-triOH-BP) (300mg・kg^<-1>・day^<-1>) for 7 days. Testosterone significantly increased the expression of kallikrein S3, cystatin-related protein-1 (CRP-1) and prostatein C3 mRNAs in the VP, and prostate secretory protein of 94 amino acids (PSP94) mRNA, but not stem cell growth factor (SCGF) mRNA, in the DP. Coad-ministration of flutamide blocked the testosterone-induced increases of all three mRNAs in the VP, but not that of PSP94 mRNA in the DP. Coad-ministration of fenitrothion significantly reduced the testosterone-induced increase of kallikrein S3 mRNA, while fenthion significantly increased the testosterone-induced increase of PSP94 mRNA. 2,4,4′-TriOH-BP significantly increased the testosterone-induced increases of CRP-1 and prostatein C3 mRNAs. These results indicate that the effects of environmental chemicals on the prostate are very complex. The Hershberger assay alone appears to be inadequate for risk assessment, and it may be useful to employ androgen-responsive genes as additional markers.
- 公益社団法人日本薬学会の論文
- 2007-08-01
著者
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OHTA Shigeru
Graduate School of Biomedical Sciences, Hiroshima University
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FURUNO Nobuaki
Institute for Amphibian Biology, Graduate School of Science, Hiroshima University
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Shigeyuki Kitamura
Nihon Pharmaceutical University
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Kitamura Shigeyuki
広島大学 医学部総合薬学科生体機能分子動態学
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Kitamura Shigeyuki
広島大学 総合薬
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Kitamura Shigeyuki
広島大学原爆放射能医学研究所
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Furuno Nobuaki
Institute For Amphibian Biology Graduate School Of Science Hiroshima University
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Kitamura Shigeyuki
Nihon Pharmaceutical University
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Sugihara K
Graduate School Of Biomedical Sciences Hiroshima University
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Suzuki T
Departments Of Analytical Biochemistry Meiji Pharmaceutical University
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Suzuki T
Department Of Xenobiotic Metabolism And Molecular Toxicology Institute Of Pharmaceutical Sciences Hi
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Fujimoto Nariaki
Research Institute For Radiation Biology And Medicine Hiroshima University
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Suzuki Tomoharu
Graduate School of Biomedical Sciences, Hiroshima University
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Ohta S
Graduate School Of Biomedical Sciences Hiroshima University
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Kitamura Shigeyuki
Institute Of Pharmaceutical Science. Hiroshima University School Of Medicine
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Fujimoto N
Research Institute For Radiation Biology And Medicine Hiroshima University
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Tsujino Seiichi
Department Of Peripheral Nervous System Research National Institute Of Neuroscience Ncnp
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Ohta Shigeru
Graduate School Of Biomedical Sciences Hiroshima Univ.
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