| Budget Amount *help |
¥23,010,000 (Direct Cost: ¥17,700,000、Indirect Cost: ¥5,310,000)
Fiscal Year 2015: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2014: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2013: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
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| Outline of Final Research Achievements |
An endocrine-disrupting chemical bisphenol A (BPA) induces adverse low-dose effects in reproductive organs and in brains. The molecular mechanisms of low-dose effects are unclear, because the binding of BPA to ERα or ERβ is very weak. We found that the transcription activity of ERα induced by BPA is remarkably reinforced by the co-existence of estrogen-related receptor α (ERRα). We have hypothesized that the ERα dimer binds to estrogen response elements (EREs) on DNA at multiple consecutive sites, which are separated at specific intervals, and induces synergistic activation. We therefore plan to explore the optimized nucleotide spacer length between the hormone response elements for ERα-ERRα synergistic transcriptional function. We found that the greatest ERα-ERRα synergistic transcriptional activation was detected with 11 bp-spacer nucleotides. We also analyzed the ER and ERR mRNA expression levels in several cell lines. Their expression levels were different in each cell.
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