生长分化因子-8在多囊卵巢综合症患者颗粒细胞调控芳香化酶表达的作用及分子机制

生长分化因子8(GDF8)参与多种生殖活动的调节。芳香化酶(AROM)促进雄激素向雌激素转化，在多囊卵巢综合症(PCOS)患者的低表达可导致其高雄激素血症。但GDF8是否参与PCOS患者AROM表达的调控未见报道。我们前期研究发现行体外受精技术助孕的PCOS患者取卵日卵泡液中的GDF8浓度高于非PCOS患者，且GDF8在PCOS患者颗粒细胞抑制AROM表达，在非PCOS患者则促进AROM表达，据此我们提出假说：GDF8在PCOS患者的高表达抑制AROM产生，从而导致PCOS高雄激素血症；此外，GDF8在PCOS患者调控AROM表达的分子机制与非PCOS患者不同。本课题选取来源于PCOS和非PCOS患者的颗粒细胞，在受体、胞内信号通路及转录因子水平上使用信号通路抑制剂或小干扰RNA技术对比研究GDF8调控AROM的分子机制，为探索GDF8在预防和治疗PCOS高雄激素中的作用提供新的思路。

Growth differentiation factor-8 is involved in multiple reproductive activities. Aromatase (AROM) is the enzyme responsible for conversion of androgens to estrogens. The abnormal expression of AROM will result in steroidogenesis disorder, such as the excessive level of androgen in Polycystic Ovary Syndrome (PCOS) patients. However, whether GDF-8 is involved in the regulation of AROM expression in granulosa cells from PCOS patients is totally unknown. Our preliminary results showed that the concentration of GDF-8 in the follicle fluid of PCOS patients is much higher than that in normal patients. Furthermore, treatment with GDF-8 up-regulated AROM expression in cultured granulosa cells from non-PCOS patients, while GDF-8 down-regulated AROM expression in PCOS patients. Accordingly, it is proposed that the inhibition of GDF-8 on AROM expression may lead to excessive androgen of PCOS patients. Furthermore, the molecular mechanism of GDF-8 in the regulation of aromatase expression in PCOS and non-PCOS patients is different. In the current study, by using granulosa cells from PCOS and non-PCOS patients, through inhibitor or siRNA techniques, we will clarify the function of growth differentiation factor-8 on the aromatase expression in granulosa cells derived from PCOS patients and the underlying molecular mechanism on different aspects, including receptors, signaling pathways and transcript factors. The results obtained from this proposed study will provide not only important insights into the molecular mechanisms mediating GDF-8-regulated aromatase expression in PCOS patients, but also a novel clinical target that could be used for the prevention and treatment of excessive androgen of PCOS.