Abstract：
OBJECTIVE: To determine the relationship between serum total testosterone (TT) levels and oxidative stress indices in patients with polycystic ovary syndrome (PCOS), and to investigate the effect of oxidative stress on androgen synthesis and its mechanism in rat ovarian theca-interstitial (T-I) cells.
METHODS: Clinical, hormonal, metabolic, and oxidative stress parameters were analyzed in a cross-sectional case-control study including 626 patients with PCOS and 296 controls. The effects of oxidized low-density lipoprotein (ox-LDL) and oxidized high-density lipoprotein (ox-HDL) on cell proliferation, TT secretion, and expression of key enzymes involved in testosterone synthesis were evaluated in T-I cells.
RESULTS: Serum TT levels were elevated with an increase in ox-LDL levels, whereas glutathione concentrations were lower in the high-TT subgroup than in the low-TT subgroup. The average ovarian volume and ox-LDL and malondialdehyde levels were significant predictors of TT levels in the multivariate regression models. In a rat ovarian T-I cell model, lipoprotein and oxidized lipoprotein treatments stimulated proliferation and promoted testosterone secretion. The mRNA and protein levels of 17α-hydroxylase were significantly higher in oxidized lipoprotein-treated cells than those in lipoprotein-treated cells. The mRNA levels of cholesterol side chain cleavage enzyme and steroidogenic acute regulatory protein were also significantly higher in ox-HDL-treated cells than in HDL-treated cells.
CONCLUSIONS: Oxidative stress can promote androgen production by up-regulating the expression of testosterone synthesis-related enzymes in vitro and may be an essential factor in elevating serum TT levels in patients with PCOS.
METHODS: Clinical, hormonal, metabolic, and oxidative stress parameters were analyzed in a cross-sectional case-control study including 626 patients with PCOS and 296 controls. The effects of oxidized low-density lipoprotein (ox-LDL) and oxidized high-density lipoprotein (ox-HDL) on cell proliferation, TT secretion, and expression of key enzymes involved in testosterone synthesis were evaluated in T-I cells.
RESULTS: Serum TT levels were elevated with an increase in ox-LDL levels, whereas glutathione concentrations were lower in the high-TT subgroup than in the low-TT subgroup. The average ovarian volume and ox-LDL and malondialdehyde levels were significant predictors of TT levels in the multivariate regression models. In a rat ovarian T-I cell model, lipoprotein and oxidized lipoprotein treatments stimulated proliferation and promoted testosterone secretion. The mRNA and protein levels of 17α-hydroxylase were significantly higher in oxidized lipoprotein-treated cells than those in lipoprotein-treated cells. The mRNA levels of cholesterol side chain cleavage enzyme and steroidogenic acute regulatory protein were also significantly higher in ox-HDL-treated cells than in HDL-treated cells.
CONCLUSIONS: Oxidative stress can promote androgen production by up-regulating the expression of testosterone synthesis-related enzymes in vitro and may be an essential factor in elevating serum TT levels in patients with PCOS.
摘要：
目的：探讨多囊卵巢综合征(PCOS)患者血清总睾酮(TT)水平与氧化应激指标的关系。并探讨氧化应激对大鼠卵巢卵泡膜间质（T-I）细胞雄激素合成的影响及其机制。
方法：临床，荷尔蒙，新陈代谢，在一项横断面病例对照研究中分析了氧化应激参数,该研究包括626例PCOS患者和296例对照.氧化低密度脂蛋白(ox-LDL)和氧化高密度脂蛋白(ox-HDL)对细胞增殖的影响,TT分泌，在T-I细胞中评估参与睾酮合成的关键酶的表达。
结果：血清TT水平随着ox-LDL水平的升高而升高，而高TT亚组的谷胱甘肽浓度低于低TT亚组。在多元回归模型中，平均卵巢体积和ox-LDL和丙二醛水平是TT水平的重要预测因子。在大鼠卵巢T-I细胞模型中,脂蛋白和氧化脂蛋白治疗刺激增殖并促进睾酮分泌。氧化脂蛋白处理的细胞中17α-羟化酶的mRNA和蛋白质水平明显高于脂蛋白处理的细胞。在ox-HDL处理的细胞中，胆固醇侧链裂解酶和类固醇生成急性调节蛋白的mRNA水平也明显高于HDL处理的细胞。
结论：氧化应激可通过体外上调睾酮合成相关酶的表达促进雄激素的产生，可能是PCOS患者血清TT水平升高的重要因素。
方法：临床，荷尔蒙，新陈代谢，在一项横断面病例对照研究中分析了氧化应激参数,该研究包括626例PCOS患者和296例对照.氧化低密度脂蛋白(ox-LDL)和氧化高密度脂蛋白(ox-HDL)对细胞增殖的影响,TT分泌，在T-I细胞中评估参与睾酮合成的关键酶的表达。
结果：血清TT水平随着ox-LDL水平的升高而升高，而高TT亚组的谷胱甘肽浓度低于低TT亚组。在多元回归模型中，平均卵巢体积和ox-LDL和丙二醛水平是TT水平的重要预测因子。在大鼠卵巢T-I细胞模型中,脂蛋白和氧化脂蛋白治疗刺激增殖并促进睾酮分泌。氧化脂蛋白处理的细胞中17α-羟化酶的mRNA和蛋白质水平明显高于脂蛋白处理的细胞。在ox-HDL处理的细胞中，胆固醇侧链裂解酶和类固醇生成急性调节蛋白的mRNA水平也明显高于HDL处理的细胞。
结论：氧化应激可通过体外上调睾酮合成相关酶的表达促进雄激素的产生，可能是PCOS患者血清TT水平升高的重要因素。
