Peroxisome Proliferator-activated Receptor-γ agonists Prevent Tumor Necrosis Factor-α-mediated Inhibition of FSH-induced Follicle Development and Estradiol Production in A PreantralFollicle Culture System

抄録

Although 60–80% of the women with polycystic ovary syndrome (PCOS) ovulate with clomiphene citrate (CC), the rest are CC-resistant. Recently, the use of insulin-sensitizing agents such as metformin and pioglitazone have been proposed for inducing ovulation in CC-resistant women with PCOS, and we have reported that administration of bezafibrate, a lipid-lowering fibrate, in addition to CC, successfully induced ovulation in CC-resistant women with PCOS and dyslipidemia. Both pioglitazone and bezafibrate are peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists. This paper reviews the evidence for the direct effects of the drugs, which are PPAR-γ agonists, on follicle development and steroidogenesis, collected using an in vitro mouse preantral follicle culture system. We used the in vitro follicle culture system with the addition of tumor necrosis factor-alpha (TNF-α), which plays a role in insulin resistance, as a model for studying follicle development in women with PCOS. TNF-α inhibited FSH-induced follicle development and steroidogenesis in the follicle culture system. Both pioglitazone and bezafibrate prevented TNF-α-mediated inhibition of FSH-induced follicle development and steroidogenesis through the PPAR-γ-stimulating pathway. Our results suggest that insulin-sensitizing drugs, especially PPAR-γ agonists, may directly influence follicle development and steroidogenesis in women with PCOS.