Polycystic Ovary Syndrome and Insulin Physiology: An Observational Quantitative Serum Proteomics Study in Adolescent, Normal-Weight Females.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with insulin resistance, even in the absence of overweight/obesity. The aim of the present study is to examine the global serum proteomic profile of adolescent, normal-weight females with PCOS in order to gain novel insight in the association of this endocrine disorder with insulin physiology and to identify novel circulating markers that can guide intervention protocols. METHODS: Non-depleted serum from normal-weight (BMI: 18-23 kg m-2 ), adolescent females (13-21 years old) with PCOS (n = 20) is compared to BMI- and age-matched healthy controls (n = 20) using our 3D quantitative proteomics methodology. Serum samples from study participants are randomly pooled to form four biological replicates of females with PCOS and four of healthy controls (n = 5 per sample pool). RESULTS: One-hundred and twenty-six proteins are differentially expressed in females with PCOS compared to controls. Gene ontology analysis shows significant enrichment for terms related to inflammatory immune response, metabolism and insulin-like growth factor receptor signaling pathway. Circulating levels of IGF-1 and -2 and IGFBP-2, -3, and -4 are found to be lower in females with PCOS compared to healthy controls. CONCLUSIONS: The present serum proteomics study provides insight into the pro-inflammatory status and insulin dysregulation in young females with PCOS and identifies potential serological markers that can guide early intervention protocols.

Serum irisin concentrations in lean adolescents with polycystic ovary syndrome.

OBJECTIVE: To explore differences in irisin concentrations between lean adolescents with PCOS and age- and body mass index (BMI)-matched controls and examine the associations of irisin with core features of the syndrome. DESIGN: Cross-sectional study. PATIENTS: Lean females with PCOS, aged 13-21 years. MEASUREMENTS: Physical, hormonal and sonographic assessment. Irisin concentrations were measured with ELISA. RESULTS: Participants included in total 39 sedentary females (mean ± SD; age 17.3 ± 2.1 years, BMI 20.7 ± 1.3 Kg/m2 ), 23 adolescents with PCOS and 16 controls. Adolescents with PCOS compared to controls had significantly elevated concentrations of fasting serum irisin (mean ± SD; PCOS, 1.7 ± 1.0 µg/mL vs controls, 1.0 ± 0.4 µg/mL; P = .007), luteinizing hormone (LH), oestradiol, testosterone, Δ4-androstenedione, 17-hydroxyprogesterone, glucose, as well as free androgen index, Ferriman-Gallwey score and mean ovarian volume (MOV). For the total sample, circulating irisin was positively correlated with MOV (r = .332, P = .041), glucose (r = .428, P = .007), insulin (rs  = .369, P = .021) and HOMA-IR (rs  = .422, P = .007) and negatively correlated with QUICKI (r = -.329, P = .041). Follicle-stimulating hormone (B = 0.295, Beta = .342, P = .042) and MOV (B = 0.182, Beta = 0.821, P = .001) were positive predictors, and LH (B = -0.108, Beta = -0.523, P = .010) and testosterone (B = -0.431, Beta = -0.457, P = .032) were negative predictors of irisin concentrations, whereas irisin positively predicted fasting glucose (B = 0.262, Beta = 0.428, P = .007). In the PCOS group, irisin concentrations were positively correlated with HOMA-IR (rs  = .416, P = .048) but negatively correlated with LH (rs  = -.499, P = .015), testosterone (r = -.585, P = .003), free androgen index (r = -.426, P = .048) and Ferriman-Gallwey score (r = -.533, P = .015). CONCLUSIONS: Irisin was associated with the adolescents' metabolic and reproductive characteristics and the hyperandrogenic phenotype of the syndrome. Much research is needed to ascertain mechanisms of elevated serum irisin in adolescent PCOS.