Figure 2: Mechanisms of estrogen action: binding and dimerization of ERs by E2 trigger nongenomic, genomic, and mitochondrial effects. Nongenomic effects may be mediated by E2-ER or by E2 bound to GPER by activating signaling molecules like MAPK, PI3K, G-proteins, and more to elicit immediate actions. Genomic effects are mediated by nuclear translocation of E2-ER complex and either (1) direct binding with estrogen response elements (ERE) along with coactivators to form a transcription complex or (2) binding to transcriptional coactivators to induce gene transcription indirectly. ERs may also localize to mitochondria to induce potentially genomic and nongenomic actions, the mechanisms of which are not well understood.