Correlation Between MTOR/RPS6 Signaling Pathway And PCOS

[Objective]To investigate the role and mechanism of mTOR/RPS6 signaling pathway in ovary of polycystic ovary syndrome?PCOS?.[Method]40 female SD rats were randomly divided into three groups:normal control group,saline control group and PCOS group.Letrozole-induced PCOS rat model by intragastric administration of letrozole for three weeks.The body weight and estrous cycle of rats in each group were monitored regularly.To confirm PCOS model has been successfully built,the serum levels of estradiol(E₂),testosterone?T?and insulin?I?were measured,the ovarian weight was recorded and the morphological changes of ovarian were observed.Immunohistochemistry and Western blot were used to detect the expression of mTOR,RPS6 and their phosphorylation,the expression of PCNA protein in ovary.At the same time,the apoptosis of follicular cells were dected by TUNEL method.The cultured ovarian granulosa cells were treated with inhibitor?Rapamycin?of mTOR and its agonist?MHY1485?.The apoptosis of granulosa cells were detected before and after treatment.[Result]In the experimental group,rats were constructed with letrozole,their estrous cycle disordered,their weight and ovarian quality increased obviously and serum hormone levels were disordered.Ovarians showed polycystic changes.These results indicated that the PCOS model was successfully constructed.Compared to normal control group and saline control group,the expression of mTOR and phosphorylation level in the ovary of PCOS group increased significantly,while the phosphorylation level of RPS6decreased significantly,the apoptosis of ovarian granulosa cells PCOS group increased,the expression of PCNA protein in theca cells and stromal cells was up-regulated.The expression of mTOR and RPS6 and their phosphorylated proteins were detected in?KGN?of human ovarian granulosa cells cultured in vitro.The phosphorylation level of mTOR was higher than that of RPS6,but the phosphorylation level of RPS6 was lower.After treatment with MHY1485 the apoptosis of granulosa cells increased while treatment with Rapamycin,the apoptosis of granulosa cell decreased.[Conclusion]Abnormal activation of mTOR signaling pathway may affect the development of follicles by promoting apoptosis of granulosa cells and proliferation of membrane cells,leading to the occurrence of PCOS.