| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Outline of Final Research Achievements |
Post-translational acute regulation of aromatase responsible for non-genomic actions of estrogens was studied. Microsomal aromatase in JEG-3 cells was rapidly inactivated and subsequently degraded in the presence of cytosol fraction, calcium, and ATP. Experiments using various kinase and phosphatase inhibitors, and siRNAs indicated that aromatase is regulated acutely at the catalytic level and subsequently at the enzyme content level by phosphorylation/dephosphorylation.
In nerve cells, a major site of non-genomic actions of estrogens, aromatase activity was suppressed within 10 min after glutaminergic stimulations, whereas it was enhanced by GABAergic, noradrenergic, and serotonergic stimulations. The degradation was suppressed by proteasome inhibitor, MG132. The knockdown and siRNA inhibition revealed the involvement of ER-associated heat shock protein/ubiquitination and then proteasome systems in the rapid degradation of the phosphorylated aromatase in nerve cells.
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