Decreased serum MG53 levels are associated with SHBG and androgen excess in women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by hormonal and metabolic abnormalities. Mitsugumin-53 (MG53), a multifunctional E3 ubiquitin ligase, is implicated in insulin signaling and oxidative stress regulation, yet its role in PCOS remains unclear. This study aimed to investigate serum MG53 levels in women with PCOS and explore their associations with hormonal, metabolic, and ovarian parameters. In this case-control study, 64 women with PCOS and 64 healthy controls with comparable age were enrolled. Serum MG53 concentrations were measured by ELISA. Associations between MG53 and continuous variables were assessed using Spearman's rank correlation. Independent determinants of MG53 were evaluated using multivariable linear regression (including age and BMI as covariates), and diagnostic performance for PCOS was assessed using receiver operating characteristic (ROC) analysis. Serum MG53 concentrations were lower in women with PCOS than in controls (median [IQR]: 124.4 [104.25-202.15] vs. 206.4 [131.63-316.58] pg/mL; p = 0.001). MG53 correlated positively with sex hormone-binding globulin (SHBG) (ρ = 0.274, p = 0.002) and inversely with ovarian follicle count (ρ = - 0.223, p = 0.011). In multivariable analysis, SHBG remained an independent positive determinant of MG53, whereas hirsutism and follicle count were independent negative predictors. MG53 demonstrated modest discrimination for PCOS (AUC = 0.667, 95% CI 0.569-0.762), with 57.8% sensitivity and 75.0% specificity at an exploratory cut-off of 131.1 pg/mL. Serum MG53 is reduced in PCOS and is associated with SHBG and features related to androgen excess and ovarian morphology. These cross-sectional findings support MG53 as a candidate biomarker reflecting metabolic-reproductive associations in PCOS; however, its diagnostic performance is modest and requires external validation.Trial registration Prospectively registered on ClinicalTrials.gov (NCT07094776) as an observational study.