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目的:探讨多囊卵巢综合征(PCOS)患者颗粒细胞中Smad2蛋白是否参与过氧化物酶体增殖物激活受体(PPARγ)对细胞色素P450芳香化酶(P450arom)的调控作用。方法:选择雄激素正常的PCOS患者10例(NA-PCOS组,A组)、伴高雄血症的PCOS患者10例(HA-PCOS组,B组)、输卵管因素致不孕患者10例(对照组,C组);测定各组患者的基础血清性激素水平;提取各组患者颗粒细胞,分别给予不同浓度罗格列酮(RSG)进行干预并加入雄烯二酮培养,用RT-PCR测定PPARγ、P450arom mRNA表达,Western blotting测定Smad2、p-Smad2蛋白的表达。结果:1 C组的P450arom mRNA相对表达量(0.823±0.094)显著高于A组(0.537±0.059)和B组(0.322±0.035),PPARγmRNA表达量(0.176±0.025)显著低于A组(0.381±0.045)和B组(0.587±0.068),差异均有统计学意义(P<0.05)。2随着RSG浓度的增加(0 nmol/L、1 nmol/L、10 nmol/L),A、B、C组P450arom mRNA表达水平、p-Smad2蛋白水平均下降,其中B组的变化最明显(P<0.05)。结论:PPARγ激动剂可能影响TGF-β/Smads信号途径,通过阻碍Smad2蛋白磷酸化从抑制P450arom的表达。
Objective: To investigate whether Smad2 is involved in the regulation of cytochrome P450 aromatase (P450arom) by peroxisome proliferator - activated receptor (PPARγ) in granulosa cells from patients with polycystic ovary syndrome (PCOS). Methods: 10 PCOS patients with normal androgen (NA-PCOS group, A group), 10 PCOS patients with hyperaemia (HA-PCOS group, B group) and 10 patients with tubal infertility Group C, group C). The basal serum levels of sex hormones were determined in each group. The granulosa cells of each group were extracted and treated with different concentrations of rosiglitazone (RSG) respectively. The cells were incubated with androstenedione. The expression of PPARγ , P450arom mRNA expression, Western blotting determination of Smad2, p-Smad2 protein expression. Results: The relative expression level of P450arom mRNA in group C was significantly higher than that in group A (0.537 ± 0.059) and group B (0.322 ± 0.035) (0.176 ± 0.025) ± 0.045) and group B (0.587 ± 0.068), the difference was statistically significant (P <0.05). 2 With the increase of RSG concentration (0 nmol / L, 1 nmol / L, 10 nmol / L), P450arom mRNA expression level in group A, B and C decreased and the level of p-Smad2 protein decreased (P <0.05). CONCLUSION: PPARγ agonists may affect the TGF-β / Smads signaling pathway and inhibit the P450arom expression by blocking Smad2 phosphorylation.