Effects of pioglitazone on E2 secretion in PCOS ovarian granulosa cells / 西安交通大学学报(医学版)

ABSTRACT

Objective To observe the effects of pioglitazone on secretion of E2 and expressions of P450 aromatase (P450arom), insulin-receptor substrate-1 (IRS-1), and insulin-receptor substrate-2 (IRS-2) mRNA in polycystic ovary syndrome (PCOS) ovarian granulosa cells.Methods In this study, granulosa cells that were fertilization-embryo transferred from 27 PCOS patients were primary cultured in vitro with different concentrations of pioglitazone (0, 10, 102, 103 and 104nmol/L) (Group A), different concentrations of pioglitazone+FSH (50ng/L, Group B) and different concentrations of pioglitazone+insulin-like growth factor I (IGF-I, 50ng/L, Group C).Estradiol concentrations in the culture supernatant were detected by radioimmunoassay;P450arom, IRS-1 and IRS-2 mRNA expressions on granulosa cells were detected by Real-time PCR.Results The levels of E2 secreted by granulosa cells and the expression of P450arom mRNA on granulosa cells of PCOS for 48 hours were different among Groups A, B and C (P<0.05).With increase in pioglitazone concentration, the level of E2 and the expression of P450arom mRNA declined, some of which correlated negatively with the concentration of pioglitazone.Among these groups, the level of E2 secretion and the expression of P450arom mRNA were higher in Group C than in Group B (P<0.01) and Group A (P<0.01) at the same concentration of pioglitazone.The level of E2 secretion and the expression of P450arom mRNA were higher in Group B than in Group A (P<0.05) at the same concentration of pioglitazone.The expressions of IRS-1 and IRS-2 mRNA on granulosa cells of PCOS under pioglitazone stimulation for 48 hour were different among the groups of different pioglitazone concentrations (P<0.05).With increase inpioglitazone concentration, the expression of IRS-1 mRNA on granulosa cells of PCOS was decreased, but the expression of IRS-2 mRNA on granulosa cells of PCOS was increased.Conclusion Pioglitazone may decrease estrogen production by inhibiting p450 aromatase and adjusting the expressions of IRS-1 and IRS-2 on granulosa cells of PCOS to play a role in ovulation induction and ameliorate insulin resistance in ovary of PCOS.Pioglitazone can inhibit IGF-I and FSH in inducing E2 secretion by ovarian granulosa cells.