卵巢黄素化颗粒细胞瘦素信号转导分子STAT3磷酸化在多囊卵巢综合征发病中的作用

Phosphorylation Expression of Leptin Receptor Signal Transduction Molecule STAT3 in Granulosa Cells from Patients with Polycystic Ovary Syndrome

目的:探讨瘦素在多囊卵巢综合征(PCOS)发病中的作用。方法:选择行IVF-ET治疗的30例PCOS患者根据体重指数(BMI)分为肥胖者(BMI≥24)15例和非肥胖者(BMI<24)15例,及同期排卵功能正常或单纯输卵管因素不孕的非PCOS肥胖者和非肥胖者各15例,采用ELISA检测各组血清瘦素水平;采用放射免疫法检测各组空腹血清胰岛素(FIN)水平;采用葡萄糖氧化酶法测定各组空腹血糖(FPG)水平,利用稳态模型(HOMA)计算胰岛素抵抗指数(即HOMA-IR);采用Western blotting检测卵巢黄素化颗粒细胞信号转导分子STAT3磷酸化水平;同法检测不同浓度的瘦素(0ng/ml、10ng/ml、100ng/ml、1000ng/ml)体外对正常人卵巢黄素化颗粒细胞STAT3磷酸化(p-STAT3)的影响。结果:①血清瘦素水平PCOS肥胖者最高,其后依次为对照组肥胖者、PCOS非肥胖者和对照组非肥胖者,各组之间两两比较,差异均具有显著性(P<0.05);②PCOS患者血清瘦素水平与BMI和HOMA-IR均呈显著正相关(r=0.707,P<0.01;r=0.761,P<0.01);③STAT3水平肥胖PCOS组最高,其后依次为肥胖对照组、非肥胖PCOS组和正常对照组,各组间两两比较,差异均具有显著性(P<0.05);④正常人卵巢黄素化颗粒细胞经不同浓度瘦素处理48h后,p-STAT3水平呈不同程度增加,至瘦素浓度达到100ng/ml时,p-STAT3水平达到高峰,随后呈下降趋势。结论:瘦素可能通过激活JAK2/STAT3信号传导通路参与PCOS排卵障碍的发生。

Objective： To explore the molecular mechanism of leptin role in polycystic ovary syndrome （PCOS）. Methods： Granulosa cells were collected from the follicular fluid of 15 obese and nonobese PCOS patients, 15 obese and nonobese women without PCOS who were undergoing IVF-ET. Serum leptin levels were measured by ELISA. Phosphorylation expression of STAT3 in granulosa cells were assessed by Western blotting. Meanwhile, in vitro effect of leptin with different concentrations （0 ng/ml, 10 ng/ml, 100 ng/ml, 1 000 ng/ml） on phosphorylation expression of STAT3 in granulosa cells were also studied by Western blotting. Results： （1）The leptin level in the follicular fluid from obese PCOS patients was significantly higher than those in other groups. There was no diffierence of leptin level between nonobese PCOS patients and nonobese women without PCOS. （2）The leptin level in the follicular fluid was significantly correlated with BMI in the 4 groups. （3）There was no difference of protein expression of STAT3 in granulosa cells in obese and nonobese PCOS patients, obese and nonobese women without PCOS. The phosphorylation expression of STAT3 in granulosa cells of obese PCOS patients were significantly higher than that in other groups （P〈0.05）; which of nonobese PCOS was also absolutly increased compared with nonobese women without PCOS （P〈0.05）. （4）Leptin stimulated the phosphorylation expression of STAT3 in granulosa cells in a time- and dose-dependent manner, but had no effect on the protein expression of STAT3 in granulosa cells. Conclusion： It is suggested that leptin may be involved in physiopathology of PCOS and cause anovulation by activation of JAK2/STAT3 signaling pathways.