多囊卵巢综合征患者卵巢颗粒细胞雄激素受体剪接变异体对内分泌激素水平的影响

Effect of ovar ian granulosa cell androgen receptor splice variant on endocr ine hor mone levels in patients with polycystic ovary syndrome

目的·探讨多囊卵巢综合征(polycystic ovarian syndrome,PCOS)患者卵巢颗粒细胞雄激素受体插入型剪接变异体(androgen receptor splice variant insertion isoform,AR-ins)对性激素及胰岛素水平的影响。方法·纳入2017年6月—2018年6月于上海交通大学医学院附属国际和平妇幼保健院辅助生殖科行体外受精-胚胎移植的154例PCOS患者(PCOS组)和79例正常排卵患者(对照组)。通过病史摘录收集其社会人口学信息、血清基础性激素及胰岛素数据,其中激素水平由化学发光法检测。收集所有患者的卵巢颗粒细胞及卵泡液。采用巢式PCR鉴定PCOS患者卵巢颗粒细胞中的雄激素受体剪接变异体,进一步将PCOS组患者分为PCOS野生型(wild type,Wt)组(39例)和PCOS AR-ins组(115例)。利用化学发光法检测3组患者卵泡液中的性激素及胰岛素水平,计算游离雄激素指数(free androgen index,FAI)。采用One-way ANOVA、Welch's ANOVA、Kruskal-Wallis H检验和χ^2检验比较3组患者的社会人口学信息、血清及卵泡液的性激素及胰岛素水平的差异。结果·与对照组相比,PCOS AR-ins组患者血清中性激素结合球蛋白(sex hormone-binding globulin,SHBG)水平显著降低(P=0.000),总睾酮(total testosterone,TT)水平(P=0.000)、胰岛素水平(P=0.001)及FAI(P=0.000)均显著增高。分别与对照组和PCOS Wt组相比,PCOS AR-ins组患者卵泡液中SHBG、TT、胰岛素水平及FAI间的差异均具有统计学意义(均P<0.05)。结论·存在AR-ins的PCOS患者血清中具有高雄激素和高胰岛素的特点,而在其卵巢局部此效应更为显著。

Objective·To investigate the effects of ovarian granulosa cell androgen receptor splice variant insertion isoform(AR-ins)on the levels of sex hormones and insulin in patients with polycystic ovary syndrome(PCOS).Methods·Seventy-nine control patients(control group)of normal ovulation and one hundred and fifty-four PCOS patients(PCOS group)who received in vitro fertilization embryo transfer in the Assisted Reproductive Department of the International Peace Maternity&Child Health Hospital,Shanghai Jiao Tong University School of Medicine from Jun.2017 to Jun.2018 were recruited.The sociodemographic information,serum basic hormones and insulin data were collected according to medical history record,and the hormone levels were measured by chemiluminescence.The ovarian granulosa cells and follicular fluids of all the patients were collected.Nested PCR was used to identify the androgen receptor splice variant(AR SV)in the ovarian granulosa cells from PCOS patients,and then they were divided into two groups,i.e.,PCOS Wt group(n=39)and PCOS AR-ins group(n=115).The levels of sex hormones and insulin in follicular fluids of the three groups were detected by chemiluminescence.The free androgen index(FAI)was calculated.The sociodemographic information,the levels of sex hormones and insulin in serum and follicular fluid of the three groups were compared by One-way ANOVA,Welch's ANOVA,Kruskal-Wallis H test and chi-square test.Results·Compared with the control group,the levels of serum sex hormone-binding globulin(SHBG)were significantly lower in the PCOS AR-ins group(P=0.000),and the levels of serum total testosterone(TT)(P=0.000),insulin(P=0.001)and FAI(P=0.000)were significantly higher in the PCOS AR-ins group.Compared with the control group and the PCOS Wt group,the differences of SHBG,TT,insulin levels and FAI in the follicular fluid in the PCOS AR-ins group were statistically significant(all P<0.05).Conclusion·PCOS patients with AR-ins have high androgen and insulin levels in serum,and this effect is more pronounced in the ovarian local microenvironment.