Biochemical or clinical changes of hyperandrogenism are important elements of polycystic ovary syndrome （PCOS）. There is currently no consensus on the definition and diagnostic criteria of hyperandrogenism in PCOS. The aim of this study was to investigate the complex symptoms of hyperandrogenic disorders and the correlations between metabolism and hyperandrogenism in patients with PCOS from an outpatient reproductive medicine clinic in China. We conducted a case control study of 125 PCOS patients and 130 controls to evaluate differences in body mass index （BMI）, total testosterone （TT）, modified Ferriman-Gallwey hirsutism score, sex hormone binding globulin （SHBG）, homeostasis model assessment-estimated insulin resistance （HOMA-IR） and free androgen index （FAI） between PCOS patients and controls and subgroups of PCOS. The prevalence of acne and hirsutism did not differ significantly between the hyperandrogenic and non-hyperandrogenic subgroup. Patients with signs of hyper- androgenism had significantly higher BMI （P 〈 0.05）, but differences in TT, SHBG, FAI and waist/hip ratio were insignificant. The odds ratio of overweight was calculated for all PCOS patients. Our results suggest that PCOS patients with high BMI tend to have functional disorders of androgen excess; therefore, BMI may be a strong pre-dictor of hyperandrogenism in PCOS.
Chun YuanXiaoqiang LiuYundong MaoFeiyang DiaoYugui CuiJiayin Liu
Set(patient SE translocation)在1992年以set-can融合基因的形式为人们所知,其参与调控DNA复制、核小体装配、组蛋白修饰、DNA转录和细胞凋亡等多个生物过程,并作为原癌基因促肿瘤发生。SET蛋白在多种组织细胞中广泛表达;在肾上腺及性腺的类固醇合成细胞中,能够通过抑制蛋白磷酸酶2(PP2A),正向调控细胞色素P450 17α羟化酶(P450c17)的裂解酶活性,最终促进雄激素的合成。SET蛋白的丝氨酸(Ser)位点磷酸化介导SET的胞质聚集,并增强SET与下游蛋白的结合力,在阿尔茨海默病(AD)、肿瘤发生等多种病理过程中发挥作用。现已发现的SET结合蛋白,功能涉及代谢、信号传导、核酸转录及翻译等多种生物学过程。已有很多研究着眼于SET结合蛋白,从而发现了SET新的生物学功能。多种肿瘤抑制剂通过与SET结合使SET蛋白失活,提高PP2A活性,最终抑制肺癌、乳腺癌等多种肿瘤的生长和转移。综述SET蛋白结构、磷酸化及SET相互作用蛋白,并总结以SET为靶向标记的抗肿瘤药物。
Objective:To investigate expressions of hypoxia-inducible factors-la(HIF-la),transforming growth factor-β1 (TGF-pl),mucinl(Mucl) and matrix metalloproteinase-9(MMP-9) in the placenta collected from the preeclampsia patients and normal pregnant women,so as to explore the possible pathophysiological mechanism of preeclampsia. Methods:The placenta villus tissues were obtained from 35 preeclampsia women,including 16 mild preeclampsia and 19 severe preeclampsia,and 20 normal pregnant women,within 5 minutes after placental expulsion.Expressions of HIF-1α,TGF-β1,Mucl and MMP-9 were detected by Western blot.Cellular location was observed by immunohistochemistry. Results:(1) HIF-1αwas mainly located in cytoplasm and nucleus of placental villous syncytiotrophoblast. Expression level of HIF-la in the severe preeclampsia group was significantly higher than that in the mild group or control group(P<0.01).(2) TGF-pl was located in the trophoblast cell and exuviates membrane.Expression level of TGF-pl in the severe and mild preeclampsia groups was significantly higher than that in control group (P<0.05).(3) Mucl was located in trophoblast cell and exuviates membrane.Expression level of MUC1 in the severe preeclampsia group was significantly higher than that in the mild preeclampsia group and control group(P< 0.01).(4) MMP-9 was located in the trophoblast cell and villous stroma,exuviates membrane.Expression levels of MMP-9 in the two preeclampsia groups were lower than that in control group(P>0.05). Conclusion:Expressions of HIF-lα,TGF-β1 and Mucl increased in the placenta of preeclampsia group,while MMP-9 decreased.Mucl can be induced and regulated by HIF-la and TGF-β1.Over-expression of Mucl in placenta can significantly suppress the activation of MMP-9,which may influence the infiltration of trophoblast cells.The increased expression of HIF-lαand TGF-β1 in placenta may induce higher level of Mucl.This study helped us to understand the pathophysiological mechanism of preeclampsia.
