title: Selective ovary resistance to insulin signaling in women with polycystic ovary syndrome.
abstract: OBJECTIVE
  Insulin resistance is a common feature of both polycystic ovary syndrome (PCOS) and non-insulin-dependent diabetes mellitus (NIDDM); however, the persistent reproductive disturbances appear to be limited to the former, suggesting that insulin resistance in the ovary itself may confer this susceptibility.
  
  
  METHODS
  Prospective study.
  
  
  METHODS
  University-affiliated department.
  
  
  METHODS
  Forty-four women undergoing IVF treatment, of whom 11 had polycystic ovaries and 33 had normal ovulation (NO).
  
  
  METHODS
  The various effects and signaling of insulin and insulin-like growth factor-1 (IGF-1) were examined in cultured ovarian granulosa cells treated with troglitazone (1 microg/mL) or with vehicle by reverse transcription-polymerase chain reaction, western blot, and in vitro functional analyses.
  
  
  METHODS
  Glycogen and DNA syntheses, mRNA and protein expression, and cellular localization of insulin/IGF-1 receptors and insulin receptor substrates (IRSs).
  
  
  RESULTS
  There were significant decreases in insulin-stimulated glucose incorporation into glycogen in PCOS cells, which is a metabolic action of insulin. However, IGF-1 stimulation was found to be greater in PCOS cells at all experimental concentrations with respect to thymidine incorporation compared with NO cells, which is a mitogenic action. Troglitazone increased the insulin-induced glycogen synthesis but reduced the IGF-1-augmented responses of DNA synthesis in PCOS cells to the range within those of NO granulosa cells. We then found that troglitazone treatment reversed the expression imbalance between IRS-1 and IRS-2 in PCOS cells.
  
  
  CONCLUSIONS
  There is a selective defect in insulin actions in PCOS granulosa cells, which suggests ovarian insulin resistance, and this metabolic phenotype is associated with an enhanced IGF-1 mitogenic potential. Troglitazone could divergently alter expression of various IRS molecules and insulin actions and could be used as an ovarian insulin sensitizer and mitogen/steroidogenic inhibitor in PCOS.
authors.affiliation: Department of Obstetrics and Gynecology, School of Clinical Medicine, Jinling Hospital of Nanjing University, Nanjing, China. xiaokewu2002@sina.com
authors.forename: Xiao Ke
authors.initials: XK
authors.lastname: Wu
authors.forename: Shan Ying
authors.initials: SY
authors.lastname: Zhou
authors.forename: Jin Xia
authors.initials: JX
authors.lastname: Liu
authors.forename: Pasi
authors.initials: P
authors.lastname: Pöllänen
authors.forename: Kirsimarja
authors.initials: K
authors.lastname: Sallinen
authors.forename: Marjaana
authors.initials: M
authors.lastname: Mäkinen
authors.forename: Risto
authors.initials: R
authors.lastname: Erkkola
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D005260:Female; D005947:Glucose / Q000378:metabolism; D006107:Granulosa Cells / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D010053:Ovary / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D010750:Phosphoproteins / Q000235:genetics; D011085:Polycystic Ovary Syndrome / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics; D011972:Receptor, Insulin / Q000235:genetics; D015398:Signal Transduction; D045162:Thiazolidinediones / Q000494:pharmacology; D000077288:Troglitazone
chemical_list: D002839:Chromans; C526292:IRS1 protein, human; C526297:IRS2 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D045162:Thiazolidinediones; D007334:Insulin-Like Growth Factor I; D004247:DNA; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin; D000077288:Troglitazone; D005947:Glucose