Comparison of mitochondrial peptide levels in patients with polycystic ovary syndrome and healthy women

Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in women of reproductive age characterized by androgen excess, ovulatory dysfunction, and polycystic ovarian morphology. Although pathophysiology of PCOS has not yet been fully elucidated, it has been suggested that mitochondrial dysfunction and associated chronic inflammation might play a role in the pathogenesis of the syndrome similar to other metabolic diseases. Humanin is a 24 amino acid long mitochondria-derived peptide encoded by the 16S ribosomal RNA gene MT-RNR2 from the mitochondrial genome. Humanin is secreted from mitochondria in response to oxidative stress and protects the cell from apoptosis and inflammation. Humanin has been shown to be reduced in metabolic diseases as an indicator of mitochondrial dysfunction. This study aimed to investigate the role of humanin in the pathophysiology of PCOS by comparing the serum humanin levels of PCOS patients and healthy control women. Forty PCOS patients and 40 age- and BMI-matched healthy controls were included. Participants were evaluated by physical examination, hormonal, biochemical, anthropometric measurements, body composition analyses, and serum humanin measurements The results of the study showed significantly increased waist circumference, waist/hip ratio, total testosterone, FAI, LDL, triglycerides, 120min insulin during 75gr OGTT in the PCOS group compared to controls. The humanin levels were significantly lower in the PCOS group than the control group (p<0.001). Humanin was positively correlated with age (r=0.455, p<0.001); and showed negative correlations with total testosterone, 120min insulin during OGTT, total cholesterol, LDL, non-HDL cholesterol and triglycerides [(r=-0.275, p=0.013), (r=-0.266, p=0.017), (r=-0.306, p=0.006), (r=-0.292, p=0.009), (r=-0.241, p=0.032), (r=-0.261, p=0.020)].In conclusion, humanin levels are decreased in PCOS suggesting mitochondrial dysfunction. Humanin levels show association with androgen excess, insulin resistance and dyslipidemia. A better understanding of the potential roles of humanin and other mitochondrial peptides in the pathophysiology of PCOS may enable the development of new treatment options for mitochondrial dysfunction in the future.