多囊卵巢综合征患者子宫内膜胰岛素抵抗的分子机制

Molecular Mechanisms of Insulin Resistance in Endometrium of Patients with PCOS

目的研究多囊卵巢综合征(PCOS)患者子宫内膜胰岛素受体底物1(IRS-1)、底物2(IRS-2)蛋白表达及酪氨酸磷酸化的程度,探讨PCOS患者子宫内膜胰岛素抵抗(IR)的分子机制。方法采用放射免疫法检测PCOS合并IR患者15例(PCOS IR组)、PCOS非IR患者15例(PCOS非IR组)和正常妇女10例(对照组)的血清黄体生成素(LH)、卵泡刺激素(FSH)、睾酮及空腹血清胰岛素(FIN)水平;利用稳态模型(HOMA)计算胰岛素抵抗指数(HOMA-IR);采用蛋白印迹法(Western blot)检测子宫内膜IRS-1和IRS-2的蛋白表达;采用免疫沉淀法检测IRS-1和IRS-2酪氨酸磷酸化程度,并进行分析比较。结果①PCOS合并IR组患者血清LH[(15.2±2.6)U/L]、LH/FSH[(2.4±0.4)]及睾酮[(2.6±0.3)nmol/L]均明显高于对照组[分别为(5.8±2.5)U/L,(0.8±0.3),(1.0±0.2)nmol/L],差异均有统计学意义(均P<0.05);PCOS合并IR组FIN[(13.8±3.1)μU/mL]、HOMA-IR(3.2±1.4)均明显高于PCOS非IR组[(6.4±3.8)μU/mL,(1.7±0.8)]及对照组[(6.5±1.9)μU/mL,(1.6±0.8)],差异均有统计学意义(均P<0.05);②PCOS合并IR组IRS-1和IRS-2蛋白表达均明显低于PCOS非IR组和对照组(均P<0.01);PCOS非IR组与对照组比较差异无统计学意义(均P>0.05);③PCOS合并IR组IRS-1和IRS-2蛋白酪氨酸磷酸化程度均明显低于PCOS非IR组和对照组(均P<0.01);PCOS非IR组与对照组比较差异无统计学意义(均P>0.05)。结论 PCOS合并IR患者子宫内膜组织的IRS-1和IRS-2蛋白表达及酪氨酸磷酸化程度降低导致受体后信号转导障碍,可能参与了PCOS子宫内膜IR的发生。

Objective To investigate the tyrosine phosphorylation and protein expression of insulin receptor substrate 1 and 2（IRS-I,IRS-2）in endometrium from patients with polycystic ovary syndrome（PCOS）, and explore the molecular mechanisms of insulin resistance（IR）in endometrium of patients with PCOS. Methods Serum and endometrium samples from patients with PCOS with IR（n=15）,PCOS without IR（n= 15）and controls（n= 10）were collected. Serum luteinizing hormone（LH）,follicle stimulating hormone（FSH）, testosterone（T）and fasting insulin（FIN）were measured by radioimmunoassay. Fasting plasma glucose（FPG）was measured by oxidase assay. IR index was calculated using homeostasis model assessment（HOMA）. The expression of IRS-1 and IR-2 was assessed by Western blot. The tyrosine phosphorylation was measured by immunoprecipitation. Results ①The serum levels of LH, LH/FSH and T in PCOS with IR were significantly higher than those in control group （all P〈0.05）. There was no significant difference between PCOS with IR and PCOS without IR（all P〉0. 05）. The serum FIN and HOMA IR in PCOS with IR were significantly higher than those in PCOS without IR and control group（all P〈0.05）. There was no significant difference between PCOS without IR and control group（all P〉0. 05）;②The protein expression of IRS-1 and IRS2 in PCOS with IR was significantly decreased compared to that in PCOS without IR and controls（all P〈0.01 ）. There was no significant difference between PCOS without IR and controls（all P〉0. 05）③The tyrosine phosphorylation of IRS-1 and IRS-2 in PCOS with IR was significantly decreased compared to that in PCOS without IR and controls（all P〈0. 01）. There was no significant difference between PCOS without IR and controls（all P〉0. 05）. Conclusion The signal transduction malfunction because of protein expression and tyrosine phosphorylation of IRS in endometrium may be one of mechanisms leading to IR in endometrium from patients with PCOS.