title: Mifepristone attenuates human chorionic gonadotropin-induced extracellular signal-regulated kinase 1/2 phosphorylation, cyclooxygenase-2, and prostaglandin E2 production in human granulosa luteal cells.
abstract: OBJECTIVE
  To elucidate the role of RU486 in regulating the function of granulosa luteal cells and its possible involvement in ovarian dysfunction.
  
  
  METHODS
  An in vitro study.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  Our subjects were women under the age of 40 who were unable to get pregnant as a result of male-factor infertility.
  
  
  METHODS
  HCG and RU486 were added to cultured granulosa luteal cells; after incubation for 12 hours, the harvested cells were subjected to total mRNA and protein measurements.
  
  
  METHODS
  Reverse transcriptase-polymerase chain reaction, immunoblot assay, immunocytochemistry, and enzyme immunoassay were performed.
  
  
  RESULTS
  RU486 attenuates hCG-induced cyclooxygenase-2 (COX-2) mRNA and protein expression and extracellular signal-regulated kinase (ERK) 1/2 phosphorylation and decreases the hCG-induced prostaglandin E2 (PGE2) production in a dose-dependent manner. RU486 treatment had no significant effect on COX-1 mRNA expression.
  
  
  CONCLUSIONS
  Treatments using gonadotropins are able to induce ERK1/2 phosphorylation resulting in increased COX-2 protein expression and prostaglandin synthesis. RU486 attenuates the activation of ERK1/2, decreases the expression of COX-2, and affects PGE2 production by inhibiting hCG-induced COX-2 expression.
authors: Department of Obstetrics and Gynecology, Graduate Institute of Medicine, College of Medicine, Kaohsiung, Taiwan, Republic of China.
authors: Eing-Mei
authors: EM
authors: Tsai
authors: Te-Fu
authors: TF
authors: Chan
authors: Yung-Hung
authors: YH
authors: Chen
authors: Shih-Cheng
authors: SC
authors: Hsu
authors: Chiao-Ya
authors: CY
authors: Chuang
authors: Jau-Nan
authors: JN
authors: Lee
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005419:Flavonoids / Q000494:pharmacology; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008184:Luteal Cells / Q000187:drug effects* / Q000378:metabolism; D015735:Mifepristone / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D006063:Chorionic Gonadotropin; D004791:Enzyme Inhibitors; D005419:Flavonoids; D006727:Hormone Antagonists; D012333:RNA, Messenger; D015735:Mifepristone; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one