Abstract: There is a significant decline in the estrogen levels in preeclampsia, and exogenous administration of estradiol normalizes blood pressure and other associated symptoms of preeclampsia. The decrease in estrogen levels may be due to changes in enzyme activities of hydroxysteroid (17-β) dehydrogenase 1, aromatase, and COMT. There is also a decrease in the novel, estrogenic G-protein-coupled receptor 30 (GPR30) in the placental trophoblast cells in preeclampsia. The activation of GPR30 protects the placenta from hypoxia-reoxygenation injury, decreases apoptosis and increases proliferation through eNOS and PI3K-Akt signaling pathways. Estrogens may also increase Ca²⁺-activated K⁺ channel function, decrease the release of inflammatory cytokines, and oxidative stress to improve placental perfusion. Both preclinical and clinical studies show the decrease in the 2-methoxyestradiol levels in preeclampsia, which may be due to a decrease in estradiol itself along with a decrease in the enzymatic actions of the COMT enzyme. 2-Methoxyestradiol activates HIF1α and vascular endothelial growth factor receptors (VEGFR-2) to maintain placental perfusion by increasing angiogenesis. The present review discusses the preclinical and clinical studies describing the role of estrogen in preeclampsia along with possible mechanisms.
Keywords: estradiol, oxidative stress, hypertension, inflammation, perfusion