Females live longer than males in many species, including humans, and estrogens are in part responsible for this protection against aging. We reported previously that estrogens can protect rats against oxidative stress, by inducing antioxidant and longevity-related genes. Thus, this study was aimed at confirming the ability of estrogens to upregulate antioxidant and longevity-related genes in humans. For this purpose, we selected 16 women of reproductive age (18-42 years old) undergoing a fertility treatment that includes a medically induced menopause, at the Valencian Infertility Institute. We took blood samples at each time point of the treatment (basal, induced menopause, estrogen, and estrogen plus progesterone replacement therapy). mRNA expression of antioxidant and longevity-related genes in peripheral blood mononuclear cells (PBMC) was determined by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Determination of reduced glutathione (GSH) in total blood was carried out using high-performance liquid chromatography (HPLC). As expected, we found that medically induced menopause significantly decreased sexual hormone (estrogens and progesterone) levels. It also lowered glutathione peroxidase (GPx), 16S rRNA, P21, and TERF2 mRNA expression and blood GSH levels. Estrogen replacement therapy significantly restored estrogen levels and induced mRNA expression of manganese superoxide dismutase (MnSOD), GPx, 16S rRNA, P53, P21, and TERF2 and restored blood GSH levels. Progesterone replacement therapy induced a significant increase in MnSOD, P53, sestrin 2 (SENS2), and TERF2 mRNA expression when compared to basal conditions. These findings provide evidence for estrogen beneficial effects in upregulating antioxidant and longevity-related genes in women.

中文翻译：

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雌激素替代疗法在医学诱导绝经后诱导女性体内的抗氧化和长寿相关基因

在包括人类在内的许多物种中，女性的寿命比男性长，而雌激素在一定程度上起到了防止衰老的作用。我们之前报道过，雌激素可以通过诱导抗氧化和长寿相关基因来保护大鼠免受氧化应激。因此，本研究旨在确认雌激素上调人类抗氧化和长寿相关基因的能力。为此，我们在巴伦西亚不孕症研究所选择了 16 名育龄妇女（18-42 岁）接受生育治疗，包括药物诱导的绝经。我们在治疗的每个时间点采集血液样本（基础、诱导绝经、雌激素和雌激素加孕激素替代疗法）。通过实时逆转录酶-聚合酶链反应（RT-PCR）测定外周血单个核细胞（PBMC）中抗氧化和长寿相关基因的mRNA表达。使用高效液相色谱法 (HPLC) 测定全血中的还原型谷胱甘肽 (GSH)。正如预期的那样，我们发现医学诱导的更年期显着降低了性激素（雌激素和黄体酮）水平。它还降低了谷胱甘肽过氧化物酶 (GPx)、16S rRNA、P21 和 TERF2 mRNA 表达和血液 GSH 水平。雌激素替代疗法显着恢复了雌激素水平，并诱导了锰超氧化物歧化酶 (MnSOD)、GPx、16S rRNA、P53、P21 和 TERF2 的 mRNA 表达，并恢复了血液 GSH 水平。孕酮替代疗法导致 MnSOD、P53、sestrin 2 (SENS2)、与基础条件相比， TERF2 mRNA 表达。这些发现为雌激素在上调女性抗氧化和长寿相关基因方面的有益作用提供了证据。