Fig. 1

Genomic and non-genomic actions of E2. E2 can regulate gene expression and activity of signaling molecules by binding to ERs via genomic and/or non-genomic pathways. In genomic regulation, binding of E2 to the ER promotes the formation of homo/hetero dimers, translocation to the nucleus and direct binding to estrogen response elements (ERE), or to transcription factors which regulate transcription of its target genes including VEGF, a pro-angiogenic factor. In non-genomic regulation, binding of E2 to ERs and GPR30 at the plasma membrane leads to activation of MAPK/ERK/PI3K/cAMP, which induce gene expression including eNOS, a potent vasodilator. E2 also binds to ERs localized on the mitochondrial membrane improving mitochondrial function by decreasing ROS production and increasing cell survival. Local E2 biosynthesis from the conversion of T to E2 via aromatase (CYP450) is also shown. Genomic pathways are shown in red arrows, whereas non-genomic pathways are shown in blue arrows. Abbreviations: E2 estrogen, ER estrogen receptor, ERE estrogen response element, T testosterone, GPCR G-protein-coupled receptor, PI3K phosphoinositide 3-kinase, MAPK mitogen activated protein kinase, AKT protein kinase B, VEGF vascular endothelial growth factor