title: Comprehensive assessment of expression of insulin signaling pathway components in subcutaneous adipose tissue of women with and without polycystic ovary syndrome.
abstract: OBJECTIVE
  Insulin resistance is a common feature of polycystic ovary syndrome (PCOS). The insulin signaling pathway consists of two major pathways, the metabolic and the mitogenic cascades. The many components of these pathways have not been comprehensively analyzed for differential expression in insulin-responsive tissues in PCOS. The goal of this study was to determine whether the core elements of the insulin signal transduction cascade were differentially expressed in subcutaneous adipose tissue (SAT) between PCOS and controls.
  
  
  METHODS
  Quantitative real-time PCR for 36 insulin signaling pathway genes was performed subcutaneous adipose tissue from 22 white PCOS and 13 healthy controls.
  
  
  RESULTS
  Genes in the insulin signaling pathway were not differentially expressed in subcutaneous adipose tissue between PCOS and controls (P>0.05 for all). Components mainly of the mitogenic pathway were correlated with both androgens and metabolic phenotypes. Expression levels of five genes (MKNK1, HRAS, NRAS, KRAS, andGSK3A) were positively correlated with total testosterone level (ρ>0,P<0.05). Inverse correlation was found between expression of six genes (HRAS, MAP2K2, NRAS, MAPK3, GRB2, andSHC1) and metabolic traits (body mass index, fasting glucose, fasting insulin, and HOMA-IR) (ρ<0,P<0.05).
  
  
  CONCLUSIONS
  Differential expression of core insulin signaling pathway components in subcutaneous adipose tissue is not a major contributor to the pathogenesis of PCOS. Correlation between clinical phenotypes and expression of several genes in the mitogenic limb of the insulin signaling pathway suggests mitogenic signaling by insulin may regulate steroidogenesis and glucose homeostasis.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
authors.forename: Ning
authors.initials: N
authors.lastname: Xu
authors.affiliation: Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Geller
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Jones
authors.affiliation: Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Funari
authors.affiliation: Departments of Obstetrics and Gynecology and Medicine, Georgia Regents University, Augusta, Georgia 30901 USA.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Azziz
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.
authors.forename: Mark O
authors.initials: MO
authors.lastname: Goodarzi
keywords: PCOS; adipose tissue; gene expression; insulin signaling pathway