| Department of Biochemistry, Faculty of Science, The M. S. University of Baroda, Vadodara, 390 002, Gujarat, India.| Department of Biochemistry, Faculty of Science, The M. S. University of Baroda, Vadodara, 390 002, Gujarat, India.| Nova IVI Fertility, Behind Xavier's Ladies Hostel, 108, Swastik Society Rd, Navrangpura, Ahmedabad, 390009, Gujarat, India.| Nova IVI Fertility, Behind Xavier's Ladies Hostel, 108, Swastik Society Rd, Navrangpura, Ahmedabad, 390009, Gujarat, India.| Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, Department of Physiology and Pathophysiology, Winnipeg MB, Canada.| Department of Biochemistry, Faculty of Science, The M. S. University of Baroda, Vadodara, 390 002, Gujarat, India. Electronic address: sglmescrl@gmail.com. |
Abstract
Insulin resistance (IR) is one of the significant aberrations in polycystic ovarian syndrome (PCOS), however is only observed in 70%-80% of obese PCOS and 20%-25% of lean PCOS. Hyperinsulinemia accompanies PCOS-IR along with hyperandrogenemia against normal insulin and androgen levels in PCOS-non insulin resistance (NIR). This could possibly be due to defects in the downstream signaling pathways. The study thus aims to unravel insulin and steroidogenic signaling pathways in luteinized granulosa cells isolated from PCOS-IR and NIR vs matched controls. Luteinized granulosa cells from 30 controls and 39 PCOS were classified for IR based on a novel method of down regulation of protein expression of insulin receptor-beta (INSR- beta) as shown in our previous paper. We evaluated expression of molecules involved in insulin, steroidogenic signaling and lipid metabolism in luteinized granulosa cells followed by analysis of estradiol, progesterone and testosterone in follicular fluid. Protein expression of INSR- beta, pIRS (ser 307), PI(3)K, PKC-zeta, pAkt, ERK1/2, pP38MAPK and gene expression of IGF showed differential expression in the two groups. Increased protein expression of PPAR-gamma was accompanied by up regulation in SREBP1c, FAS, CPT-1 and ACC-1 genes in PCOS-IR group. Expression of StAR, CYP19A1, 17 beta- HSD and 3 beta- HSD demonstrated significant decrease along with increase in CYP11A1, FSH-R and LH-R in both the groups. Follicular fluid testosterone increased and progesterone decreased in PCOS-IR group. This study shows how candidate molecules that were differentially expressed, aid in designing targeted therapy against the two phenotypes of PCOS. |
