Antigoni Manousopoulou1, Nasser M Al-Daghri2, Shaun Sabico2, Diana J Garay-Baquero1, Jie Teng1, Amal Alenad1, Majed S Alokail2, Nikos Athanasopoulos3, Efthymios Deligeoroglou3, George P Chrousos3, Flora Bacopoulou3, Spiros D Garbis1,4,5. 1. Institute for Life Sciences, University of Southampton, Southampton, UK. 2. Chair for Biomarkers of Chronic Diseases, Biochemistry Department, King Saud University, Kingdom of Saudi Arabia. 3. Center for Adolescent Medicine and UNESCO Chair on Adolescent Health Care, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, Aghia Sophia Children's Hospital, Athens, Greece. 4. Cancer Sciences, Faculty of Medicine, Southampton General Hospital, University of Southampton, UK. 5. Proteome Exploration Laboratory, Beckman Institute, Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
Abstract
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.
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.
Authors: Diana J Garay-Baquero; Cory H White; Naomi F Walker; Marc Tebruegge; Hannah F Schiff; Cesar Ugarte-Gil; Stephen Morris-Jones; Ben G Marshall; Antigoni Manousopoulou; John Adamson; Andres F Vallejo; Magdalena K Bielecka; Robert J Wilkinson; Liku B Tezera; Christopher H Woelk; Spiros D Garbis; Paul Elkington Journal: JCI Insight Date: 2020-09-17