Research Information System
JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION, 2025 (SCI-Expanded, Scopus)
Purpose Humanin is a mitochondria-derived peptide (MDP) secreted in response to oxidative stress and linked to diverse cellular processes including inflammation and insulin resistance (IR). In a PCOS rat model, humanin has been shown to be downregulated in polycystic ovaries, and exogenous humanin supplementation has attenuated IR and ovarian morphological abnormalities. We aimed to investigate the role of humanin in the pathophysiology of PCOS by comparing serum and skeletal muscle tissue profiles in women with PCOS and healthy women. 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 from a subset of patients and controls who consented to the procedure. Results 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)]. Western blot analysis showed no significant difference in skeletal muscle humanin levels between PCOS and control groups (p = 0.71). Serum humanin showed negative correlations with testosterone, 2 h insulin during OGTT, total cholesterol, LDL, and triglycerides. Conclusion Serum humanin levels are decreased in PCOS suggesting mitochondrial dysfunction that appears to be associated with androgen excess, IR and lipids. Reduction of circulating humanin is unlikely to be linked to an alteration of this MDP in the skeletal muscle which constitutes the majority of the mitochondrial reserve in the body.