title: Changes in the expression of insulin signaling pathway molecules in endometria from polycystic ovary syndrome women with or without hyperinsulinemia.
abstract: Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder associated with insulin resistance and compensatory hyperinsulinemia. Scarce information is available on the expression of molecules involved in the insulin pathway in endometria from women with PCOS. Therefore, we examined the protein levels of insulin-signaling molecules, like insulin receptor, insulin-receptor substrate (IRS)-1, pIRS-1Y612, Akt, AS160, pAS160T642 and GLUT4 in endometria from PCOS women with or without hyperinsulinemia. Protein levels were assessed by Western blot and immunohistochemistry in 21 proliferative-phase endometria from control women (CE = 7), normoinssulinemic PCOS women (PCOSE-NI = 7) and hyperinsulinemic PCOS women (PCOSE-HI = 7). The data show no differences in the expression of insulin receptor between all groups as assessed by Western blot; however, IRS-1 and pIRS-1Y612 were lower in PCOSE-HI than controls and PCOSE-NI (P < 0.05). AS160 was detected in all analyzed tissues with similar expression levels between groups. Importantly, PCOSE-HI exhibited lower levels of pAS160T642 (P < 0.05) and of GLUT4 (P < 0.05) compared with CE. The immunohistochemistry for insulin receptor, IRS-1, Akt, AS160 and GLUT4 showed epithelial and stromal localization; IRS-1 staining was lower in PCOSE-HI (P < 0.05). In conclusion, human endometrium has the machinery for glucose uptake mediated by insulin. The diminished expression of GLUT4, as well as the lower level of pIRS-1Y612 and pAS160T642 exhibited by PCOSE-HI, suggests a disruption in the translocation of vesicles with GLUT4 to the cell surface in these patients.
authors.affiliation: Laboratory of Endocrinology and Reproductive Biology, University of Chile Clinical Hospital, Santiago, Chile.
authors.forename: Romina
authors.initials: R
authors.lastname: Fornes
authors.forename: Paulina
authors.initials: P
authors.lastname: Ormazabal
authors.forename: Carlos
authors.initials: C
authors.lastname: Rosas
authors.forename: Fernando
authors.initials: F
authors.lastname: Gabler
authors.forename: David
authors.initials: D
authors.lastname: Vantman
authors.forename: Carmen
authors.initials: C
authors.lastname: Romero
authors.forename: Margarita
authors.initials: M
authors.lastname: Vega
mesh_terms: D000328:Adult; D015153:Blotting, Western; D048708:Cell Growth Processes / Q000502:physiology; D004717:Endometrium / Q000166:cytology / Q000378:metabolism*; D005260:Female; D020690:GTPase-Activating Proteins / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction; D018709:Statistics, Nonparametric
chemical_list: D020690:GTPase-Activating Proteins; D051275:Glucose Transporter Type 4; C526292:IRS1 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C495692:SLC2A4 protein, human; C518767:TBC1D4 protein, human; D011972:Receptor, Insulin