Kaur Sukhneeraj Pal, Bansal Seema, Chopra Kanwaljit
University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
Steroids. 2015 Apr;96:7-15. doi: 10.1016/j.steroids.2015.01.004. Epub 2015 Jan 13.
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.
大量证据表明，绝经后卵巢功能衰退与神经元功能障碍有关。其主要原因是雌激素缺乏导致氧化应激和炎性细胞因子增加。17β-雌二醇（E2，具有强大抗氧化和抗炎活性的激素）对多个器官系统具有深远的保护作用，但β-雌二醇的女性化副作用限制了其临床疗效。17α-雌二醇（E2α），一种无女性化作用的类似物，作为治疗绝经相关神经元病变的替代策略，给科学界带来了一线希望。我们评估了17α-雌二醇（5、10μg/kg）对大鼠卵巢切除术后4周认知缺陷、抑郁和运动协调的保护作用，并将其与相同剂量的E2的疗效进行比较。行为学检测后处死动物，取脑进行生化研究。还评估了子宫重量。E2和E2α（5、10μg/kg）对减轻去卵巢大鼠的认知缺陷、抑郁症状和运动不协调具有同等的保护作用。两者均表现出显著的抗氧化活性，且E2增加了血清雌二醇水平和子宫重量，这是女性化作用的标志，但E2α没有。因此可以得出结论，在预防绝经后神经病变方面，E2α是E2的安全替代品。
