| Project/Area Number |
15310043
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Risk sciences of radiation/Chemicals
|
|---|
| Research Institution | Okazaki Research Facilities, National Institute of Natural Sciences (2004)
Okazaki National Research Institutes (2003) |
|---|
Principal Investigator |
WATANABE Hajime Okazaki Research Facilities, National Research Institute of Natural Sciences, Okazaki Institute for Integrative Bioscience, Associate Professor, 岡崎統合バイオサイエンスセンター, 助教授 (80212322)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
IGUCHI Taisen Okazaki Research Facilities, National Research Institute of Natural Sciences, Okazaki Institute for Integrative Bioscience, Professor, 岡崎統合バイオサイエンスセンター, 教授 (90128588)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Project Status |
Completed (Fiscal Year 2004)
|
| Budget Amount *help |
¥15,800,000 (Direct Cost: ¥15,800,000)
Fiscal Year 2004: ¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 2003: ¥8,200,000 (Direct Cost: ¥8,200,000)
|
|---|
| Keywords | estrogen / environmental chemicals / endocrine disruptors / nonylphenol / DNA microarray / ホルモン / マウス / 免疫沈降 |
|---|
| Research Abstract |
Recently, there has been considerable concern about potential endocrine-disrupting effects of chemicals released into the environment. Those chemicals that have estrogenic activity are termed xenoestrogens or endocrine disrupters. They are thought to mimic or disturb the function of estrogen and many are known to possess estrogen receptor binding activity.
To compare the effects of physiological estrogen (estradiol) and chemicals suspected as non-physiological estrogens (diethylstilbestrol ; nonylphenol), we used DNA microarray analysis to examine the uterine gene expression patterns induced by the estrogens and chemicals. Although estradiol and diethylstilbestrol induced many genes to respond in the same way, different groups of genes showed varying levels of sensitivity to each estrogen, resulting in different dose-response patterns. These results suggested that each estrogen has a similar but distinct effect on uterine gene expression.
In contrast to the similar effects of estrogen and chemicals observed in the uterus, in liver, gene expression was more markedly affected by estrogenic chemical (nonylphenol) than by estradiol. This indicated that in the liver, nonylphenol could activate another set of genes that is distinct from estrogen-responsive genes. These results indicate that nonylphenol has very similar effects to estradiol on gene expression in uterine but not in liver tissue, indicating that tissue-specific effects should be considered in order to elucidate the distinct effects of alkylphenols. In addition, in order to understand gene activation mechanism by estrogen in genomic level, chromatin immunoprecipitation was performed to identify direct target of estrogen receptor. Correlation between immunoprecipitated DNA fragment and gene activation profile was analyzed.
|
