Sex hormones modulate circulating antioxidant enzymes: impact of estrogen therapy.

Sex hormones modulate circulating antioxidant enzymes: impact of estrogen therapy.
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DOI:
10.1016/j.redox.2013.05.003
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发表时间:
2013
期刊:
影响因子:
11.4
通讯作者:
Serviddio G
Serviddio G
中科院分区:
生物学1区
文献类型:
--
作者:
Bellanti F;Matteo M;Rollo T;De Rosario F;Greco P;Vendemiale G;Serviddio G

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卵巢衰老影响许多组织,并产生各种症状和体征。我们推测雌激素也可能通过调节细胞抗氧化酶系统的活性来影响循环氧化还原平衡。我们的目的是探讨手术雌激素剥夺和替代(ERT)对生育妇女谷胱甘肽平衡和抗氧化酶表达的影响。19名健康的绝经前妇女接受了全子宫切除术和双侧输卵管卵巢切除术,在基线、手术后30天(未使用ERT)和ERT后30天进行了评价。通过测量血液中还原型(GSH)和氧化型(GSSG)谷胱甘肽以及GSSG/GSH比值来确定氧化还原平衡。通过检测血清雌激素(E2)水平和外周血单个核细胞超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)和谷胱甘肽S-转移酶(GST)mRNA表达来评价抗氧化状态。血清E2在手术后显著降低,并且在ERT 30天后19名患者中有12名升高(应答者)。在这些患者中,手术后观察到氧化应激增加,ERT后消退。氧化应激持续减少的SOD和GSH-Px的mRNA表达,恢复治疗后30天的反应。CAT和GST mRNA的表达没有改变手术和替代治疗。更年期与抗氧化剂基因表达的显著变化相关,而抗氧化剂基因表达反过来影响循环氧化还原状态。雌激素替代疗法能够通过作为关键抗氧化剂基因表达的调节剂来预防和抵消这种修饰。这些发现表明,抗氧化基因,几乎部分,在性激素的控制下,和性别疾病的差异的病理生理学可能取决于氧化还原生物学。手术绝经导致的雌激素剥夺与抗氧化基因表达的显著变化相关,而抗氧化基因表达反过来影响循环氧化还原状态。雌激素替代疗法可以通过调节关键的抗氧化基因表达来预防和抵消氧化应激。手术绝经是女性雌激素剥夺的生理模型。更年期减少抗氧化基因的表达。雌激素替代恢复抗氧化基因表达。抗氧化基因几乎部分地受到性激素的控制。性别疾病的病理生理差异可能取决于氧化还原生物学。
Ovarian senescence affects many tissues and produces a variety of symptoms and signs. We hypothesized that estrogens may also influence circulating redox balance by regulating activity of the cellular antioxidative enzyme system. We aimed to explore the impact of surgical estrogen deprivation and replacement (ERT) on the glutathione balance and antioxidant enzymes expression in fertile women. Nineteen healthy premenopausal women who underwent total hysterectomy with bilateral salpingo-oophorectomy were evaluated at baseline, 30 days after surgery without ERT and 30 days after ERT. Redox balance was determined by measuring blood reduced (GSH) and oxidized (GSSG) glutathione, as well as the GSSG/GSH ratio. Antioxidant status was evaluated by measuring serum estrogen (E2) levels and mRNA expression of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione S-transferase (GST) in peripheral blood mononuclear cells. Serum E2 significantly lowered after surgery, and increased in 12 out of 19 patients after 30 days of ERT (Responders). In such patients, an increase in oxidative stress was observed after surgery that resolved after ERT. Oxidative stress was sustained by reduction in the mRNA expression of both SOD and GSH-Px, that recovered after 30 days of therapy in responders. CAT and GST mRNA expression were not modified by surgery and replacement therapy. Menopause is associated with significant change in antioxidant gene expression that in turn affects circulating redox state. Estrogens replacement therapy is able to prevent and counteract such modifications by acting as regulators of key antioxidant gene expression. These findings suggest that antioxidant genes are, almost in part, under the control of sex hormones, and that pathophysiology of the difference in gender disease may depend on the redox biology. Estrogen deprivation by surgical menopause is associated with significant change in antioxidant gene expression that in turn affects circulating redox state. Estrogens replacement therapy may prevent and counteract oxidative stress by regulating key antioxidant gene expression. Surgical menopause is a physiological model of estrogen deprivation in women. Menopause reduces antioxidant gene expression. Estrogen replacement restores antioxidant gene expression. Antioxidant genes are, almost in part, under the control of sex hormones. Pathophysiology of the difference in gender disease may depend on the redox biology.
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