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氧化应激增加与多囊卵巢综合征中的高雄激素血症有关,这可通过氧化脂蛋白体外刺激大鼠卵巢雄激素合成得到证实。

Increased oxidative stress is associated with hyperandrogenemia in polycystic ovary syndrome evidenced by oxidized lipoproteins stimulating rat ovarian androgen synthesis in vitro.

机构信息

Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.

Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.

出版信息

Endocrine. 2024 Jun;84(3):1238-1249. doi: 10.1007/s12020-024-03726-2. Epub 2024 Feb 19.

Abstract

PURPOSE

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.

摘要

目的

确定多囊卵巢综合征(PCOS)患者血清总睾酮(TT)水平与氧化应激指标之间的关系,并探讨氧化应激对雄激素合成的影响及其在大鼠卵巢间质(T-I)细胞中的作用机制。

方法

采用横断面病例对照研究,纳入 626 例 PCOS 患者和 296 例对照,分析临床、激素、代谢和氧化应激参数。评估氧化型低密度脂蛋白(ox-LDL)和氧化型高密度脂蛋白(ox-HDL)对 T-I 细胞增殖、TT 分泌以及参与睾酮合成的关键酶表达的影响。

结果

血清 TT 水平随 ox-LDL 水平升高而升高,而高 TT 亚组的谷胱甘肽浓度低于低 TT 亚组。卵巢平均体积和 ox-LDL、丙二醛水平是多元回归模型中 TT 水平的显著预测因素。在大鼠卵巢 T-I 细胞模型中,脂蛋白和氧化型脂蛋白处理刺激增殖并促进睾酮分泌。氧化型脂蛋白处理细胞中 17α-羟化酶的 mRNA 和蛋白水平明显高于脂蛋白处理细胞。ox-HDL 处理细胞中胆固醇侧链裂解酶和甾体急性调节蛋白的 mRNA 水平也明显高于 HDL 处理细胞。

结论

氧化应激可通过上调体外睾酮合成相关酶的表达促进雄激素生成,可能是 PCOS 患者血清 TT 水平升高的重要因素。

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