Fig. 7.

Genomic and mitochondrial effects of estrogen. In endothelial cells, estrogen binds to cytosolic ER and dissociates it from heat shock protein 90 (HSP-90). The estrogen-ER complex translocates to the mitochondria where it decreases the production of ROS and H₂O₂, reducing oxidative stress and increases oxidative phosphorylation. The estrogen-ER complex also translocates into the nucleus where it increases the expression of nuclear respiratory factor-1 (NRF-1), and in turn increases the level of nuclear encoded mitochondrial gene products. Estrogen/ER also increases the expression of fos, myc, and jun which in turn promote cell growth and proliferation. Estrogen/ER also stimulates Egr-1, which is upregulated in response to acute and chronic injury. Estrogen could also increase the gene transcription of eNOS and COX2, leading to increased production of NO and PGI₂ with consequent stimulation of vasodilation and angiogenesis.