title: Chlormadinone acetate suppresses prostaglandin biosynthesis in human endometrial explants.
abstract: OBJECTIVE
  To elucidate the mode of action of chlormadinone acetate (CMA) in reducing dysmenorrheic pain by studying the effects of CMA and dexamethasone (DEX) on messenger RNA (mRNA) abundance of cyclo-oxygenase-2 (COX-2), annexin-1 (ANXA1), glucocorticoid receptor (GR), progesterone receptor (PR), and concentrations of prostaglandin F(2α) (PGF(2α)) and leukotrienes B(4) (LTB(4)) and C(4) (LTC(4)) in human endometrial explants.
  
  
  METHODS
  Ex vivo study.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  Fifteen premenopausal patients undergoing surgery for benign gynecologic disorders.
  
  
  METHODS
  Endometrial explants were obtained by aspiration curettage and stimulated ex vivo with interleukin-1β before exposure to CMA or DEX; mRNA levels were determined via reverse transcription-quantitative real-time polymerase chain reaction, and concentrations of arachidonic acid metabolites by enzyme immunoassays.
  
  
  METHODS
  Messenger RNA levels of COX-2, ANXA1, PR, and GR; concentrations of PGF(2α), LTB(4), and LTC(4) in endometrial explants treated with CMA or DEX.
  
  
  RESULTS
  In IL-1β-treated explants COX-2 mRNA and PGF(2α), concentrations were significantly down-regulated by CMA but not by DEX. Chlormadinone acetate did not affect mRNA abundance of ANXA1, PR, and GR.
  
  
  CONCLUSIONS
  Our data suggest that CMA is a suppressor of COX-2 expression. Comparison with DEX revealed that progestin-specific activity of CMA may mainly be responsible for suppression of prostaglandin biosynthesis in human endometrium.
authors: Department of Obstetrics and Gynecology, Clinic for Endocrinology and Reproductive Medicine, University of Freiburg, Freiburg, Germany. aida.hanjalic-beck@uniklinik-freiburg.de
authors: Aida
authors: A
authors: Hanjalic-Beck
authors: Wolfgang R
authors: WR
authors: Schäfer
authors: Wolfgang R
authors: WR
authors: Deppert
authors: Lara
authors: L
authors: Fischer
authors: Antonia
authors: A
authors: Stein
authors: Laura
authors: L
authors: Seebacher
authors: Akou Seli
authors: AS
authors: von Gradowski
authors: Johanna
authors: J
authors: Stuckenschneider
authors: Hans P
authors: HP
authors: Zahradnik
mesh_terms: D000293:Adolescent; D000328:Adult; D017305:Annexin A1 / Q000235:genetics; D002715:Chlormadinone Acetate / Q000494:pharmacology*; D003280:Contraceptives, Oral, Synthetic / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D015237:Dinoprost / Q000378:metabolism; D004412:Dysmenorrhea / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D007975:Leukotriene B4 / Q000378:metabolism; D017997:Leukotriene C4 / Q000378:metabolism; D009924:Organ Culture Techniques; D011453:Prostaglandins / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics; D055815:Young Adult
chemical_list: D017305:Annexin A1; D003280:Contraceptives, Oral, Synthetic; D005938:Glucocorticoids; D053583:Interleukin-1beta; D011453:Prostaglandins; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D011980:Receptors, Progesterone; D002715:Chlormadinone Acetate; D007975:Leukotriene B4; D017997:Leukotriene C4; D003907:Dexamethasone; D015237:Dinoprost; D051546:Cyclooxygenase 2