Gender difference in cytoprotection induced by estrogen on female and male bovine aortic endothelial cells

Before menopause, women have a lower risk of cardiovascular diseases than men. Studies attribute this gender difference to estrogenic protection in the female cardiovascular system. We have demonstrated that 17 beta -estradiol (E-2) protects female bovine aortic endothelial cells against oxidative injury, probably through the induction of antioxidant enzyme activities. In this study, we examined whether E-2 confers a differential protection on male and female cells. Bovine aortic endothelial cells from both genders were preconditioned for 24 h with E-2 (1 nM to 10 muM), and their resistance to paraquat (1 mM, 3 h), a superoxide generator, was measured using an MTT assay. In contrast to the protection observed in female bovine aortic endothelial cells, there was no protective effect by E-2 on male bovine aortic endothelial cells at physiologic concentrations. However, E-2 at 1-10 muM attenuated paraquat's toxicity in both male and female cells, probably through its direct antioxidant activity. E-2 at I nM increased in female, but not in male, cells the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, which was associated with decreased levels of reactive oxygen species during subsequent paraquat exposure. This suggests that antioxidant enzyme induction plays some role in E-2-augmented oxidative resistance in female endothelial cells.