title: Estrogen Enhances Esophageal Barrier Function by Potentiating Occludin Expression.
abstract: BACKGROUND
  We recently demonstrated that a female sex hormone, estrogen, suppressed esophageal epithelial injury in a reflux esophagitis model of rat, suggesting that estrogen may play an important role in controlling the progress of the gastro-esophageal reflux disease spectrum. However, the precise mechanism of the action is unclear.
  
  
  OBJECTIVE
  To investigate the potential role of estrogen in the esophageal barrier function.
  
  
  METHODS
  Male rabbits were pretreated with either continuous release 17β-estradiol or placebo, and the excised esophageal mucosa was subjected to Ussing chamber experiments after the 2-week pre-treatment. The mucosal side of the chamber was perfused with luminal irritants (HCl or acidified sodium nitrite), while the basal side was perfused by modified Krebs buffer. The epithelial barrier function was evaluated by the transmembrane resistance and the epithelial permeability. The intercellular space of the epithelium was investigated with transmission electron microscopy and the expression of tight junction protein, occludin, claudin-1, and claudin-4, with immunoblotting.
  
  
  RESULTS
  Estrogen pre-treatment significantly attenuated the decrease in the transmembrane resistance and the increase in the epithelial permeability induced by luminal irritants. Furthermore, the dilation of the intercellular space induced by luminal HCl was significantly alleviated by 17β-estradiol administration. The baseline occludin expression was significantly potentiated by 17β-estradiol administration.
  
  
  CONCLUSIONS
  This is the first study showing an enhancement of the esophageal barrier function by 17β-estradiol administration. The lack of the protective effect of estrogen could be responsible for the male predominance of erosive reflux esophagitis.
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai, 980-8574, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Honda
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai, 980-8574, Japan. kiijima@med.tohoku.ac.jp.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Iijima
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai, 980-8574, Japan.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Asanuma
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai, 980-8574, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Ara
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai, 980-8574, Japan.
authors.forename: Takeharu
authors.initials: T
authors.lastname: Shiroki
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai, 980-8574, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kondo
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai, 980-8574, Japan.
authors.forename: Waku
authors.initials: W
authors.lastname: Hatta
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai, 980-8574, Japan.
authors.forename: Kaname
authors.initials: K
authors.lastname: Uno
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai, 980-8574, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Asano
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai, 980-8574, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Koike
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai, 980-8574, Japan.
authors.forename: Tooru
authors.initials: T
authors.lastname: Shimosegawa
mesh_terms: D000818:Animals; D004942:Esophagitis, Peptic / Q000378:metabolism*; D004947:Esophagus / Q000502:physiology*; D004958:Estradiol / Q000502:physiology*; D006851:Hydrochloric Acid; D008297:Male; D062793:Occludin / Q000378:metabolism*; D010539:Permeability; D011817:Rabbits; D011897:Random Allocation; D012727:Sex Characteristics; D012977:Sodium Nitrite
chemical_list: D062793:Occludin; D004958:Estradiol; D012977:Sodium Nitrite; D006851:Hydrochloric Acid
keywords: Dilatation of intercellular space; Epithelial permeability; Esophageal barrier function; Estrogen; Occludin