... Interestingly, estradiol may play a dual role in modulating NRF2 activity. On the one hand, its metabolites activate NRF2 via the generation of reactive oxygen species (ROS) (independent of the ER) [29]. While recent studies demonstrated that estradiol leads to an activation of NRF2 in a wide range of cell types [30,31], the estradiol effect was only noted on protein and not on mRNA levels, suggesting that the main effect of estradiol is based on NRF2 protein stabilization [32]. ... 
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