Oxidative stress promotes hyperandrogenism by reducing sex hormone-binding globulin in polycystic ovary syndrome

Abstract

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.

Keywords: HepG2 cells; Oxidative stress; hepatocyte nuclear factor-4α; polycystic ovary syndrome; sex hormone-binding globulin.