Effect Of FR180204 On ERK Serine Phosphorylation And GLUT-4 Protein Expression In Ovarian Granulosa Cells Of Polycystic Ovarian Syndrome (PCOS)

Objective:To investigate the effect of ERK protein kinase inhibitor FR180204 on ERK serine phosphorylation and GLUT-4 protein expression in ovarian granulosa cells of polycystic ovarian syndrome（PCOS）.Then explore the molecular mechanism of PCOS.Method:Ovarian granulosa cells were collected from PCOS patients undergoing in-ivtro fertilization-embryo transfer（IVF-ET）,every examples were inoculated in two culture bottles,with inhibitor of FR180204 as PCOS+IN group（n=20）,the others as PCOS group（n=20）.Those ovarian granulosa cells from non-PCOS patients undergoing IVF-ET used as control group（N-PCOS group）（n=20）.The cultured ovarian granulosa cell of three groups were examined by Western Blotting for phosphorylation of extracel ular regulated protein kinase（p-ERK）and glucose transporter-4（GLUT-4）.Result:There was no statistically significant difference in age,infertility term,BMI,bE₂,bFSH,bPRL,Gn start quantity,Gn total quantity between PCOS group and N-PCOS group（t value was 0.000,1.870,0.828,1.480,0.099,0.261,1.376,0.924,all P>0.05）;the LH,T,number of ovums of PCOS group were significantly higher than N-PCOS group,and the differences were statistically significant（t value was 7.582,4.577,2.330,all P<0.05）.There were significant differences in phosphorylation of extracellular regulated protein kinase（p--ERK）and glucose transporter-4（GLUT-4）among three groups（F value was 36.773,593.955,all P<0.05）;The phosphorylation of ERK in the granulosa cell of PCOS patients were higher than N-PCOS group.The protein expression of GLUT-4 in the granulosa cells of PCOS patients was lower than N-PCOS group（P<0.05）.The phosphorylation of ERK with FR180204 was lower significantly,the protein expression of GLUT-4 with FR180204 was lower than N-PCOS group,but was more than PCOS group（P<0.05）.Conclusion:（1）FR180204 can reduce the phosphorylation of ERK and at the same time promote GLUT-4 protein expression;（2）There is an interaction betwee n MAPK/ERK and PI3K/AKT signaling pathway,FR180204 can inhibit the activity of MAPK/ERK pathway by reducing serine phosphorylation of ERK,so as to enhance the activity of PI3K/AKT pathway in ovarian granulosa cells and further promote the expression of GLUT-4 protein;（3）The occurrence of PCOS is closely related to the abnormal activation of MAPK/ERK pathway.