Levels of Rabs and WAVE family proteins associated with translocation of GLUT4 to the cell surface in endometria from hyperinsulinemic PCOS women

• Published in: Human reproduction (Oxford) 2010-11, Vol.25 (11), p.2870-2877
• Main Authors: Rosas, C., Gabler, F., Vantman, D., Romero, C., Vega, M.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; endometrium; Endometrium - metabolism; Endometrium - secretion; Female; Glucose Transporter Type 4 - metabolism; GLUT4; Gynecology. Andrology. Obstetrics; Humans; hyperinsulinemia; Hyperinsulinism - metabolism; Medical sciences; Polycystic Ovary Syndrome - metabolism; rab GTP-Binding Proteins - metabolism; Rabs; WASP; Wiskott-Aldrich Syndrome Protein Family - metabolism; Wiskott-Aldrich Syndrome Protein, Neuronal - metabolism
• ISSN: 0268-1161; 1460-2350
• DOI: 10.1093/humrep/deq232

BACKGROUND Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder highly associated with insulin resistance and compensatory hyperinsulinemia. It is known that the insulin signaling pathway is impaired in endometria from PCOS hyperinsulinemic women, but no information is available about molecules associated with cell surface GLUT4 translocation. We therefore evaluated the protein levels of AS160 target molecules, Rab8A and Rab10, and the WAVE family proteins involved in the cortical-actin remodeling, Neural Wiskott-Aldrich Syndrome Protein (N-WASP) and WASP, in endometria from hyperinsulinemic PCOS women and controls. METHODS Protein levels were assessed by western blot, immunohistochemistry and immunofluorescence in proliferative (PE = 7) and secretory (SE = 7) phase endometria from control women and in endometria from hyperinsulinemic PCOS women (PCOS h-INS = 7). Results Similar levels were detected for Rab10 in the three studied groups; however, Rab8A levels decreased in SE (P < 0.05) while higher levels were obtained in PCOSE h-INS compared with PE (P < 0.05). In the normal menstrual cycle, Neural Wiskott-Aldrich syndrome protein (N-WASP) and WASP levels were increased in SE versus PE (P < 0.05), but in PCOSE h-INS, the levels were diminished compared with PE (P < 0.05). CONCLUSIONS SE is characterized by protein expression changes associated with glucose uptake. In endometria from PCOS women with hyperinsulinemia, reduced levels of WAVE family proteins could compromise the cell surface GLUT4 exposure and the consequent glucose uptake in this tissue.