17α-Estradiol: a candidate neuroserm and non-feminizing estrogen for postmenopausal neuronal complications

Extensive evidence suggests that decline in ovarian function with menopause is associated with neuronal dysfunction. Major cause of this is rise in oxidative stress and inflammatory cytokines because of estrogen deficiency. 17β-Estradiol (E2, hormone with potent antioxidant and anti-inflammatory activity) has profound protective actions on multiple organ systems, but feminizing side effects of β-estradiol limits its clinical efficacy. 17α-Estradiol (E2α), a non feminizing congener, gives a ray of hope to the scientific community as an alternative strategy to treat menopause associated neuronal pathologies. We assessed the protective actions of 17α-estradiol (5, 10μg/kg) against cognitive deficits, depression and motor coordination after 4weeks of ovariectomy in rats and compared its efficacy with E2 at same doses. After the behavioral assay animals were sacrificed and their brains were harvested for biochemical studies. Uterine weights were also assessed. E2 and E2α (5, 10μg/kg) were equally protective against attenuating cognitive deficits, depressive symptoms and motor incoordination in OVX rats. Both demonstrated significant antioxidant activity and E2, but not E2α, increased serum estradiol levels and proliferated uterine weights, markers of feminizing action. It can thus be concluded that E2α offers safe alternative to E2 in protecting against menopausal neuropathologies.