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.
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。