title: Expression of insulin-receptor substrate-1 and -2 in ovaries from women with insulin resistance and from controls.
abstract: OBJECTIVE
  To evaluate the role of insulin-receptor substrate (IRS)-1 and -2 in ovary dysfunction in women with insulin resistance.
  
  
  METHODS
  Immunoblotting and immunohistochemical analyses of the localization and staining intensity of IRS-1 and IRS-2 in the ovaries of women with the polycystic ovary syndrome (PCOS) and gestational diabetes mellitus.
  
  
  METHODS
  Department of Obstetrics and Gynecology, Turku University Central Hospital.
  
  
  METHODS
  Sections of ovary were obtained at the time of cesarean section from five volunteers without medical complications and three patients with gestational diabetes mellitus. Paraffin-embedded ovary sections were selected from those on file from the department of pathology; four were from women with a histologic diagnosis of PCOS and seven were from women with endometriosis (controls).
  
  
  METHODS
  None.
  
  
  METHODS
  Protein expression of IRS in human ovary samples.
  
  
  RESULTS
  Immunoblotting with specific monoclonal and polyclonal antibodies showed the presence of 165-kDa and 183-kDa proteins that corresponded to the size of IRS-1 and IRS-2, respectively, in normal pregnant ovaries and human cultured follicles. Immunohistochemical staining showed that positive IRS-2 expression in antral follicles was restricted to theca internal cells in ovulatory ovaries but was distributed widely in all compartments of follicles in different stages in polycystic ovaries. Compared with follicles at a similar stage of development in ovulatory ovaries, follicles in polycystic ovaries showed decreased staining for IRS-1 in granulosa cells but increased staining for IRS-2 in theca internal cells. These features of IRS-1 and -2 expression were also noted in preantral and atretic follicles from patients with gestational diabetes mellitus compared with those who had uncomplicated pregnancy.
  
  
  CONCLUSIONS
  This study highlights a shift of the follicular insulin signal protein from IRS-1 to IRS-2 in insulin-resistant states and suggests an association between this change and ovarian abnormality in PCOS and gestational diabetes mellitus.
authors.affiliation: Department of Obstetrics and Gynecology, University Central Hospital of Turku, Turku, Finland. xiaoke.wu@utu.fi
authors.forename: X
authors.initials: X
authors.lastname: Wu
authors.forename: K
authors.initials: K
authors.lastname: Sallinen
authors.forename: L
authors.initials: L
authors.lastname: Anttila
authors.forename: M
authors.initials: M
authors.lastname: Mäkinen
authors.forename: C
authors.initials: C
authors.lastname: Luo
authors.forename: P
authors.initials: P
authors.lastname: Pöllänen
authors.forename: R
authors.initials: R
authors.lastname: Erkkola
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D016640:Diabetes, Gestational / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance; D047908:Intracellular Signaling Peptides and Proteins; D008970:Molecular Weight; D009839:Oligomenorrhea / Q000150:complications / Q000378:metabolism; D010053:Ovary / Q000378:metabolism* / Q000473:pathology; D010750:Phosphoproteins / Q000096:biosynthesis*; D011085:Polycystic Ovary Syndrome / Q000150:complications / Q000378:metabolism; D011247:Pregnancy
chemical_list: C526292:IRS1 protein, human; C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins