Estrogen Enhances Esophageal Barrier Function by Potentiating Occludin Expression

Junya Honda, Katsunori Iijima, Kiyotaka Asanuma, Nobuyuki Ara, Takeharu Shiroki, Yutaka Kondo, Waku Hatta, Kaname Uno, Naoki Asano, Tomoyuki Koike, Toru Shimosegawa

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)


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. Aim: 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.

Original languageEnglish
Pages (from-to)1028-1038
Number of pages11
JournalDigestive Diseases and Sciences
Issue number4
Publication statusPublished - 2016 Apr 1


  • Dilatation of intercellular space
  • Epithelial permeability
  • Esophageal barrier function
  • Estrogen
  • Occludin

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology


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