CONICET | Buscador de Institutos y Recursos Humanos

Polycystic ovary syndrome, PCOS, is one of the most common metabolic disorders in the reproductive age. This syndrome is associated with hyperandrogenism and in about 50 percent of cases with hyperinsulinemia and insulin resistance. Glucotransporter 4 modulated by insulin is reduced in skeletal muscle and adipose tissue in PCOS. Metformin is the most extensively insulin-sensitizing agent used for the treatment of this pathology. This study was conducted to investigate the effects of hyperandrogenism, hyperinsulinism and metformin on glucose uptake and GLUT4 in granulosa cells. Material and Methods: Granulosa cells were isolated from follicular fluid after transvaginal aspiration, from 9 patients undergoing in vitro fertilization for male factor, after controlled ovarian hyperstimulation with rFSH and GnRH antagonist. Cells were purified by Percoll gradient and incubated two days with DMEM plus 10 percent fetal bovine serum. Then, cells were separated in eight groups and cultured in serum free DMEM with one of the following interventions for 48 hs: Results: Glucose uptake diminished significantly in I and TI compared to control group GLUT4 protein expression was strongly decreased in groups T, I and TI . However, when granulosa cells were incubated together T, I or TI with metformin, glucose uptake was not changed comparing with control uptake. Protein levels of GLUT4 were maintained similar in all metformin groups compared with control group. Conclusion: In vitro high levels of testosterone and insulin alter the glucose metabolism in granulosa cells, whereas metformin is able to prevent these effects. This study suggests that the increases of testosterone and insulin in PCOS could affect ovary glucose metabolism pathway that can be prevented with metformin administration.