title: Dienogest inhibits aromatase and cyclooxygenase-2 expression and prostaglandin E₂ production in human endometriotic stromal cells in spheroid culture.
abstract: OBJECTIVE
  To determine the effect of dienogest (DNG) on the expression of aromatase and cyclooxygenase-2 (COX-2) and the production of prostaglandin E(2) (PGE(2)) in human endometriotic stromal cells (ESCs).
  
  
  METHODS
  Experimental study in vitro.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  Seventeen patients with ovarian endometrioma.
  
  
  METHODS
  ESCs from chocolate cyst linings of ovaries were treated with DNG.
  
  
  METHODS
  Expression of aromatase and COX-2 evaluated in spheroid cultures of human ESCs by real-time quantitative polymerase chain-reaction and immunocytochemistry, production of PGE(2) quantified by enzyme-linked immunosorbent assay (ELISA), and nuclear factor kappa B (NF-κB) DNA-binding examined by ELISA and immunocytochemistry.
  
  
  RESULTS
  The pharmaceutical actions of DNG on the expression of aromatase and COX-2 and the production of PGE(2) were examined using spheroid cultures of human ESCs. More aromatase, COX-2, and PGE(2) were expressed in spheroid cultures than in conventional ESCs monolayers. In the spheroid cultures, DNG (10(-7) M) and progesterone (10(-7) M) inhibited the expression of aromatase, COX-2, and PGE(2). DNG also inhibited NF-κB DNA-binding activity and reduced the immunocytochemical protein expression of aromatase, COX-2, and NF-κB p50 nuclear localization.
  
  
  CONCLUSIONS
  Because DNG inhibits aromatase and COX-2 expression as well as PGE(2) production in ESCs, these pharmacologic features might contribute to a therapeutic effect of DNG on endometriosis.
authors: Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan.
authors: Kaoruko
authors: K
authors: Yamanaka
authors: Bing
authors: B
authors: Xu
authors: Izumi
authors: I
authors: Suganuma
authors: Izumi
authors: I
authors: Kusuki
authors: Shizuka
authors: S
authors: Mita
authors: Yutaka
authors: Y
authors: Shimizu
authors: Kiyoshi
authors: K
authors: Mizuguchi
authors: Jo
authors: J
authors: Kitawaki
mesh_terms: D000328:Adult; D001141:Aromatase / Q000235:genetics / Q000378:metabolism*; D047072:Aromatase Inhibitors / Q000494:pharmacology*; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004715:Endometriosis / Q000201:enzymology* / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D016328:NF-kappa B / Q000378:metabolism; D009277:Nandrolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D010049:Ovarian Diseases / Q000201:enzymology* / Q000235:genetics; D010053:Ovary / Q000187:drug effects* / Q000201:enzymology; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D018874:Spheroids, Cellular; D017154:Stromal Cells / Q000187:drug effects* / Q000201:enzymology; D055815:Young Adult
chemical_list: D047072:Aromatase Inhibitors; D052246:Cyclooxygenase 2 Inhibitors; D016328:NF-kappa B; D012333:RNA, Messenger; C023635:dienogest; D009277:Nandrolone; D004247:DNA; D001141:Aromatase; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone