title: Genistein-induced fluid accumulation in ovariectomised rats' uteri is associated with increased cystic fibrosis transmembrane regulator expression.
abstract: OBJECTIVE
  High genistein doses have been reported to induce fluid accumulation in the uteri of ovariectomised rats, although the mechanism underlying this effect remains unknown. Because genistein binds to the oestrogen receptor and the cystic fibrosis transmembrane regulator mediates uterine fluid secretion, we hypothesised that this genistein effect involves both the oestrogen receptor and cystic fibrosis transmembrane regulator.
  
  
  METHODS
  Ovariectomised adult female Sprague-Dawley rats were treated with 25, 50, or 100 mg/kg/day genistein for three consecutive days with and without the ER antagonist ICI 182780. One day after the final drug injection, the animals were humanely sacrificed, and the uteri were removed for histology and cystic fibrosis transmembrane regulator mRNA and protein expression analysis using real-time polymerase chain reaction and Western blotting, respectively. The cystic fibrosis transmembrane regulator protein distribution was analysed visually by immunohistochemistry.
  
  
  RESULTS
  The histological analysis revealed an increase in the circumference of the uterine lumen with increasing doses of genistein, which was suggestive of fluid accumulation. Moreover, genistein stimulated a dose-dependent increase in the expression of cystic fibrosis transmembrane regulator protein and mRNA, and high-intensity cystic fibrosis transmembrane regulator immunostaining was observed at the apical membrane of the luminal epithelium following 50 and 100 mg/kg/day genistein treatment. The genistein-induced increase in uterine luminal circumference and cystic fibrosis transmembrane regulator expression was antagonised by treatment with ICI 182780.
  
  
  CONCLUSIONS
  Genistein-induced luminal fluid accumulation in ovariectomised rats' uteri involves the oestrogen receptor and up-regulation of cystic fibrosis transmembrane regulator expression, and these findings reveal the mechanism underlying the effect of this compound on changes in fluid volume in the uterus after menopause.
authors: University of Malaya, Faculty of Medicine, Department of Physiology, Kuala Lumpur, Malaysia, University of Malaya, Faculty of Medicine, Department of Physiology, Kuala Lumpur/Malaysia.
authors: Asma
authors: A
authors: Chinigarzadeh
authors: University of Malaya, Faculty of Medicine, Department of Anatomy, Kuala Lumpur, Malaysia, University of Malaya, Faculty of Medicine, Department of Anatomy, Kuala Lumpur/Malaysia.
authors: Normadiah M
authors: NM
authors: Kassim
authors: University of Malaya, Faculty of Medicine, Department of Molecular Medicine, Kuala Lumpur, Malaysia, University of Malaya, Faculty of Medicine, Department of Molecular Medicine, Kuala Lumpur/Malaysia.
authors: Sekaran
authors: S
authors: Muniandy
authors: University of Malaya, Faculty of Medicine, Department of Physiology, Kuala Lumpur, Malaysia, University of Malaya, Faculty of Medicine, Department of Physiology, Kuala Lumpur/Malaysia.
authors: Naguib
authors: N
authors: Salleh
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000032:analysis* / Q000187:drug effects*; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D007150:Immunohistochemistry; D008593:Menopause / Q000187:drug effects; D010052:Ovariectomy; D048789:Phytoestrogens / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012016:Reference Values; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
chemical_list: D048789:Phytoestrogens; D012333:RNA, Messenger; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D019833:Genistein