title: [Ovarian insulin resistance and insulin sensitizer effect on polycystic ovary syndrome].
abstract: OBJECTIVE
  To explore the molecular defects of insulin signalling in polycystic ovary and in vitro effects of troglitazone, one of the insulin sensitizers-thiazolidinediones on polycystic ovary syndrome (PCOS).
  
  
  METHODS
  The metabolic and mitogenic effects of insulin and insulin-like growth factor 1 (IGF-1) were examined in cultured human ovarian luteinizing granulosa cells from PCOS (n = 11) and normally ovulatory (as control, n = 33) women with vehicle or troglitazone (1 microg/ml).
  
  
  RESULTS
  Basal rates were similar, but there were significant decreases in insulin-stimulated glucose incorporation into glycogen in PCOS cells, a metabolic action of insulin. However, IGF-1 response was found to be about twice greater in PCOS cells at all experimental concentrations with respect to thymidine incorporation compared to control cells, a mitogenic action. Troglitazone increased 2-3 fold the insulin-induced glycogen synthesis, but reduced the IGF-1 augmented responses of DNA synthesis in PCOS cells to within the range of control granulosa cells. As compared with control, PCOS granulosa cells had higher insulin receptor substrate 1 (IRS -1) expression, but lower IRS-2 expression. IRS-2 protein levels were increased and IRS-1 levels were reduced by troglitazone treatment, with a greater extent in the former.
  
  
  CONCLUSIONS
  There is a selective defect in insulin actions in PCOS granulosa cells, suggesting ovarian insulin resistance and this metabolic phenotype is associated with an enhanced IGF-1 mitogenic potential. Troglitazone could divergently alter signal protein expressions and thus insulin actions, as an ovarian insulin sensitizer and mitogen/steroidogenic inhibitor in PCOS.
authors.affiliation: Department of Obstetrics and Gynecology, First Affiliated Hospital, Heilongjiang Traditional Medicine University, Harbin 150040.
authors.forename: Xiao-ke
authors.initials: XK
authors.lastname: Wu
authors.forename: Erkkola
authors.initials: E
authors.lastname: Risto
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D005260:Female; D006003:Glycogen / Q000096:biosynthesis; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D010053:Ovary / Q000378:metabolism / Q000503:physiopathology*; D011085:Polycystic Ovary Syndrome / Q000378:metabolism / Q000503:physiopathology*; D015398:Signal Transduction; D013844:Thiazoles / Q000494:pharmacology*
chemical_list: D007328:Insulin; D013844:Thiazoles; D007334:Insulin-Like Growth Factor I; D006003:Glycogen