title: GnRH agonists induce endometrial epithelial cell apoptosis via GRP78 down-regulation.
abstract: BACKGROUND
  Endometriosis is a benign chronic gynecological disease that affects women of reproductive age, characterized by the presence of functional endometrial tissues outside the uterine cavity. GnRH agonists exhibit anti-proliferative and apoptosis-enhancing activities and have long been used for the treatment of endometriosis. There is a critical need to identify the signaling modules involving GnRH agonist therapy for the treatment of endometriosis. In this study, we compared the proteomic profiles of endometriosis in patients before and after GnRH agonist therapy to identify proteins that might provide further information concerning the mechanisms underlying the functions of GnRH agonists.
  
  
  METHODS
  A total of 55 protein spots with different abundances were observed using Difference Gel Electrophoresis (DIGE), and 26 of these proteins were assigned clear identities through Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Tandem Mass Spectroscopy (MALDI-TOF/TOF MS).
  
  
  RESULTS
  We validated four of these proteins through Western blotting and immunohistochemistry using human endometrial tissue. We also characterized the effect of Leuprolide acetate (LA) on the apoptosis of eutopic endometrial epithelial cells. LA treatment significantly promoted the apoptosis of eutopic endometrial epithelial cells and inhibited the expression of the anti-apoptotic factor GRP78. GRP78 knockdown enhanced LA-induced cell apoptosis, whereas, the overexpression of GRP78 in eutopic endometrial epithelial cells suppresses LA-induced apoptosis.
  
  
  CONCLUSIONS
  These results suggest that GnRH agonists induce endometrial epithelial cell apoptosis via GRP78 down-regulation. This study might provide an important molecular framework for further evaluation of GnRH agonist therapy.
authors.affiliation: Department of Pathophysiology, Key Laboratory of Proteomics of Guangdong Province, Southern Medical University, Guangzhou, China. iweihuinan@163.com.|GuangDong Women and Children Hospital, Guangzhou, China. iweihuinan@163.com.
authors.forename: Huinan
authors.initials: H
authors.lastname: Weng
authors.affiliation: GuangDong Women and Children Hospital, Guangzhou, China. liufenghua_9@163.com.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Pathophysiology, Key Laboratory of Proteomics of Guangdong Province, Southern Medical University, Guangzhou, China. hushuihuangdd@163.com.
authors.forename: Shuiwang
authors.initials: S
authors.lastname: Hu
authors.affiliation: GuangDong Women and Children Hospital, Guangzhou, China. lylylylyyyyy@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: ZhuJiang Hospital of Southern Medical University, Guangzhou, China. wyf1988@163.com.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000328:Adult; D017209:Apoptosis; D015536:Down-Regulation; D004717:Endometrium / Q000166:cytology / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D014591:Uterine Diseases / Q000188:drug therapy
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D007987:Gonadotropin-Releasing Hormone