| Project/Area Number |
17590104
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Environmental pharmacy
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| Research Institution | University of Shizuoka |
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Principal Investigator |
DEGAWA Masakuni University Shizuoka, School of Pharmaceutical Sciences, Professor, 薬学部, 教授 (50134002)
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| Co-Investigator(Kenkyū-buntansha) |
NEMOTO Kiyomitsu University Shizuoka, School of Pharmaceutical Sciences, Associate Professor, 薬学部, 准教授 (90189366)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | endocrine disruptor / species difference / sex difference / cholesterol biosynthesis / cytochrome P450 / Trp-P-1 / lead nitrate / PCB / 肝臓 / AhR / 精巣 / テストステロン / チロキシン |
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| Research Abstract |
In this project, we studied on toxic effects of endocrine disruptors and their species-, gender-, and age-related differences and obtained the results as stated below.
1. Administration of hepatocarcinogenic Trp-P-1 to male rats reduced the levels of serum total testosterone and gene expression of the testicular enzymes responsible for androgen biosynthesis and then increased the level of hepatic cytochrome P4501A1. These findings suggest that Trp-P-1 has the potential to become an endocrine disruptor.
2. Analysis with the use of UGT1A isoform-deficient mice indicated that phenobarbital-induced decrease in serum total thyroxine (T4) did not occur only through increase in hepatic T4-UDP-glucuronosyltransferase.
3. Comparative study using rats and mice indicated that there was no correlation between formation of methylsulfonyl metabolites of 2,2',4,5,5'-pentachlorobiphenyl and decrease in serum T4 level.
4. Analysis with the use of TNF-α-knockout mice revealed that lead nitrate, a possible endocrine disruptor, downregulates the expression of hepatic cholesterol 7 a-hydroxylase gene through TNF-a-independent pathway.
5. Lead nitrate induced the hepatic gene expression of sterol regulatory element binding protein-2 and 3-hydroxy-3-methylglutaryl-CoA reductase in coincidence with development of hypercholesteromia in male rats faster than in female.
6. Hepatic cytochrome P4501A subfamily enzymes were induced by the nitroanisidine isomers in rats but not the other examined rodents, mice and guinea pigs.
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