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Oxidative stress promotes hyperandrogenism by reducing sex hormone-binding globulin in polycystic ovary syndrome
Fertility and Sterility ( IF 6.6 ) Pub Date : 2021-08-22 , DOI: 10.1016/j.fertnstert.2021.07.1203
Yuan Sun 1 , Suiyan Li 2 , Hongwei Liu 3 , Huai Bai 4 , Kaifeng Hu 4 , Renjiao Zhang 4 , Qingqing Liu 4 , Ping Fan 4
Affiliation  

Objective

To determine the relationships between circulating sex hormone-binding globulin (SHBG) and oxidized low-density lipoprotein (ox-LDL), total oxidant status, total antioxidant capacity, oxidative stress index, malondialdehyde, and the high-density lipoprotein (HDL) inflammatory index in patients with polycystic ovary syndrome (PCOS) and to investigate the effect of oxidative stress on the expression of SHBG and its mechanism in HepG2 cells.

Design

Cross-sectional study.

Setting

University hospital.

Patient(s)

A total of 533 women with PCOS and 292 control women were included.

Intervention(s)

None.

Main Outcome Measure(s)

Circulating SHBG, hormones, and metabolic and oxidative stress indices were determined in all subjects. The effects of ox-LDL and ox-HDL on the mRNA and protein expression of SHBG and related transcription factors were observed in HepG2 cells.

Result(s)

The HDL inflammatory index, total oxidant status, oxidative stress index, and malondialdehyde levels were significantly higher in the three PCOS subgroups with different SHBG levels than in the controls. The ox-LDL and total antioxidant capacity were higher in the PCOS subgroups with SHBG levels <75th percentile compared with the controls or the PCOS subgroup with SHBG levels ≥75th percentile. In HepG2 cells, the SHBG concentration in the culture supernatant, the mRNA levels of SHBG and hepatocyte nuclear factor-4α (HNF-4α), and the protein levels of HNF-4α were significantly lower in ox-LDL- and ox-HDL-treated cells than in the control cells and lipoprotein-treated cells.

Conclusion(s)

Oxidative stress inhibits the expression and secretion of SHBG by downregulating HNF-4α in vitro and may be an important factor promoting the occurrence of hyperandrogenemia in PCOS.



中文翻译:

氧化应激通过减少多囊卵巢综合征中的性激素结合球蛋白来促进雄激素过多症

客观的

确定循环性激素结合球蛋白 (SHBG) 与氧化低密度脂蛋白 (ox-LDL)、总氧化状态、总抗氧化能力、氧化应激指数、丙二醛和高密度脂蛋白 (HDL) 炎症之间的关系多囊卵巢综合征(PCOS)患者的指标,并探讨氧化应激对HepG2细胞SHBG表达的影响及其机制。

设计

横断面研究。

环境

大学医院。

耐心)

总共包括 533 名患有 PCOS 的女性和 292 名对照女性。

干预措施

没有任何。

主要观察指标)

在所有受试者中测定循环 SHBG、激素以及代谢和氧化应激指数。在HepG2细胞中观察ox-LDL和ox-HDL对SHBG及相关转录因子mRNA和蛋白表达的影响。

结果)

具有不同 SHBG 水平的三个 PCOS 亚组的 HDL 炎症指数、总氧化状态、氧化应激指数和丙二醛水平显着高于对照组。与对照组或 SHBG 水平≥75% 的 PCOS 亚组相比,SHBG 水平 <75% 的 PCOS 亚组的 ox-LDL 和总抗氧化能力更高。在HepG2细胞中,ox-LDL-和ox-HDL-培养上清液中SHBG浓度、SHBG和肝细胞核因子-4α(HNF-4α)的mRNA水平以及HNF-4α的蛋白水平均显着降低。处理的细胞高于对照细胞和脂蛋白处理的细胞。

结论

氧化应激在体外通过下调HNF-4α抑制SHBG的表达和分泌,可能是促进PCOS高雄激素血症发生的重要因素。

更新日期:2021-08-22
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