FIGURE 1.

A simplified overview of the putative mechanisms involved in estrogens genomic and nongenomic actions. Genomic mechanisms involve activation of the estrogen receptors (ERα/β) by estrogen, which then translocate either to the cell nucleus or to the mitochondria resulting in transcription activation in the cell nucleus or in the mitochondria. Nongenomic mechanisms involve binding of estrogens to ERs or to a G protein coupled receptor (GPER), either at the plasma membrane or intracellularly to activate second messenger systems, such as those involving mitogen-activated protein kinase (MAPK) or cyclic adenosine 3’,5’-monophosphate (cAMP) pathways. ERα/β activation can ameliorate mitochondrial activity directly by enhancing mitochondrial functioning through promoting gene transcription of mitochondrial DNA and indirectly, by promoting gene transcription of mitochondrial and metabolic genes in the cell nucleus. NO, nitric oxide.