Endocrine Abstracts

Background and Aim: Humanin is a mitochondria-derived peptide (MDP) secreted in response to oxidative stress and linked to diverse cellular processes including inflammation and insulin resistance. Humanin has been shown to be downregulated in polycystic ovaries and exogenous humanin supplementation has attenuated insulin resistance and ovarian morphological abnormalities in a PCOS rat model. The aim of this study was to investigate the role of humanin in the pathophysiology of PCOS by comparing serum and skeletal muscle tissue profile of humanin in women with PCOS and healthy women.

Subjects and Methods: Forty women with PCOS [(mean±SD) age:21.8±2.3 years, BMI:25.0±4.8 kg/m²] and 40 age- and BMI-matched healthy controls were included. Anthropometric, hormonal, biochemical measurements and body composition analyses were carried out in all participants. Vastus lateralis muscle biopsies were analyzed for humanin expression on 6 PCOS and 6 age- and BMI-matched healthy controls within the study group.

Results: Women with PCOS showed significantly increased waist circumference, total testosterone, FAI, LDL, triglycerides, 120 min insulin during 75 gr OGTT compared to controls. Serum humanin levels were significantly lower in the PCOS group than those in controls [Median (IQR):474.9 (313.0 – 633.5) pg/ml vs 672.3 (481.7-764.6) pg/ml P<0.001)]. Humanin showed negative correlations with total testosterone, 120 min 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=0.02)]. Western blot analysis showed no significant difference in skeletal muscle humanin levels between PCOS and control groups (P=0.71).

Conclusion: Serum humanin levels are decreased in PCOS suggesting mitochondrial dysfunction that is associated with androgen excess, insulin resistance and dyslipidemia. Reduction of circulating humanin is not linked to an alteration of this MDP in the skeletal muscle which constitutes the majority of the mitochondrial reserve in the body. A better understanding of potential roles of humanin and other MDPs in the pathophysiology of PCOS may enable development of new treatment options for mitochondrial dysfunction in the future.