The Research On The Correlation Between Endometial Disorders And PI3K/AKT,MAPK/ERK Pathways Activated By Insulin In Women With Polycystic Ovary Syndrome

Objective:To investigate the roles of insulin resistance and hyperinsulinemia in women with Polycystic Ovary Syndrome(PCOS)on the formation of endometrial hyperplasia and carcinoma and the molecular mechanism of it.Method:Collected 52 patients diagnosed as PCOS as study group,32 non-PCOS patients with infertility or benign ovary tumor(without ovulation failure)as control group.They were excluded from other endocrinopathy and haven't taken any hormone drugs for 3 months.Circulating hormonal parameters were measured in all patients,insulin releasing test were measured in PCOS group and fasting blood glucose and insulin measured in controls.All of them were carried out pathological study of endometria.The PCOS patients were divided into insulin resistance and non-insulin resistance groups(groupâ… andâ…¡) respectively according to HOMA-IR,nomal and abnormal endometrium groups(group B and A) respectively according to the outcome of pathology.Western blotting method to detect the expressions of AKT,P-AKT;ERKl/2 and P-ERK1/2 in all endometria.Results:â… .Insulin resistance and other characteristics of endocrinology and metabolism in PCOS patients.i The clinical characteristics of PCOS:In this research,we found that the cardinal characteristics in PCOS patients included insulin resistance,hyperandrogenism,obesity,elevated level of LH and relatively higher ratio of LH/FSH,lower level of E₂.The incidence of insulin resistance and obesity were 73.1%,71.2%respectively,the incidence of insulin resistance in the obese was 83.8 %;the incidence of hyperandrogenism,the ratio of LH/FSH≥2 were 42.3%,55.7 %respectively.ii.Serum hormonal,metabolic parameters and BMI:The BMI of PCOS group was higher than the control P＜0.05;groupⅠ＞groupⅡ＞the control,but only the difference between groupâ… and the control was significant P＜0.05.(2)The LH level was higher in PCOS group than the control P＜0.05;groupⅡ＞groupⅠ＞the control,the diferences between groupâ…¡and groupâ… ,groupâ…¡and the control were all both significant,P＜0.05.(3)The ratio of LH/FSH is higher in PCOS group than the control,P＜0.05;groupⅡ＞groupⅠ＞the control,the differences among three groups were all significant P＜0.05.(4)Serum E₂ level was lower in PCOS than in control group P＜0.05;only the difference between groupâ… and control group was significant P＜0.05.(5)The level of testosterone was higher in PCOS group than the control group P＜0.05;groupⅠ＞groupⅡ＞the control,but only the difference between groupâ… and control group was significant P＜0.05.(6)The level of fasting insulin was higher in PCOS group,P＜0.05;the differences between groupâ… and groupâ…¡,groupâ… and control group were both significant.(7)The HOMA-IR was higher in PCOS group P＜0.05,the differences between groupâ… and groupâ…¡,groupâ… and the control were both significant P＜0.05.(8)INS-AUG was higher in groupâ… than in groupâ…¡,P＜0.05.â…¡insulin resistance and endometrial pathology:Among 52 patients of PCOS,38 of them were diagnosed with insulin resistance,of which,17 patients were divided into group A and 21 patients into group B.14 patients were without insulin resistance,of which,2 patients were divided into group A,the others into group B according to the outcome of pathology.The incidence of endomerial hyperplasia in groupâ… was higher than groupâ…¡,P＜0.05.â…¢The detection of expression AKT,ERK1/2 and P-AKT,P-ERK1/2 by Western blottingi MAPK7ERK1/2 pathway(1)The expressions of ERK1/2 and P-ERK1/2 in the endometria in both PCOS and control groups:The expressions of ERK1/2 in both PCOS and control groups were without any difference(P＞0.05),while the expression of P-ERK1/2 was significantly higher in PCOS group(P＜0.001).(2)The expressions of ERK1/2 and P-ERK1/2 in groupâ… and groupâ…¡:The expressions of ERK1/2 in groupâ… groupâ…¡were indifferent(P＞0.05),but expression of P- ERK1/2 was higher significantly in PCOS(P＜0.001).(3)The expressions of ERK1/2 and P-ERK1/2 in groupA and groupB:The expressions of ERK1/2 in groupA and groupB were indifferent(P＞0.05),but expression of P- ERK1/2 was higher in groupA(P＞0.001).(4)The factors affecting the expressions of ERK1/2 and P-ERKl/2:The expression of ERK1/2 had no correlation with BMI,E2,T,HOMA-IR,et al(P＞0.05),but the expression of P-ERK1/2 was positively correlated with BMI,T and HOMA-IR(P＜0.05).ii PI3K/AKT pathway(1)The expressions of AKT and P-AKT in the endometrial of PCOS and control groups:The expressions of AKT in both PCOS and control groups was without any difference(P＞0.05),while the expression of P-AKT was higher in PCOS group(P＜0.05).(2)The expressions of AKT and P-AKT in groupâ… and groupâ…¡:The expressions of AKT in groupâ… and groupâ…¡were indifferent(P＞0.05),but expression of P- AKT was higher in groupâ… (P＜0.05).(3)The expressions of AKT and P-AKT in groupA and groupB:The expressions of AKT in groupA and groupB were indifferent(P＞0.05),but expression of P- AKT was higher in groupA(P＜0.001).(4)The factors affecting the expressions of AKT and P-AKT:the expression of AKT had no correlation with BMI,E2,T,HOMA-IR,et al(P＞0.05),but the expression of P-AKT was positively correlated with BMI,HOMA-IR and T(P＜0.05).iii Factors affecting the endometrium pathology in PCOSThe endometrium pathology was positively correlated with HOMA-IR,BMI(r=0.449, P=0.003;r=0.324,P=0.007);meanwhile,positively correlated with P-AKT and P-ERKl/2(r=0.425,P=0.000;r=0.590,P-0.000).Conclusion:(1) hyperandroganism,insulin resistance and secondary hyperinsulinemia were all endocrinic and metabolic characteristics of PCOS.Elevated level of LH was also the important clinical characterastics and an index worthy to refer to when making diagnosis.(2)the expressions of AKT and ERK1/2 were comprehensively in the endometria of human,which were predictors of material basis of insulin cell signal transduction pathways.(3)The activation degree of AKT and ERK1/2 were both enhanced in endometrial of PCOS,the tissue homeostasis in endometia from PCOS were deregulated.(4)The enhanced activation of AKT and ERK1/2 were both positively correlated with endometrial disorders.(5)The activation of AKT,ERK1/2 pathways induced by insulin may be involved in the formation of endomerial disorders in PCOS women.(6)The insulin resistance and secondary hyperinsulinemia in PCOS were all both risk factors for endometrial disorders.