Estrogens stimulate proliferation of intrahepatic biliary epithelium in rats

Domenico Alvaro, Gianfranco Alpini, Paolo Onori, Lucia Perego, Gianluca Svegliati Baroni, Antonio Franchitto, Leonardo Baiocchi, Shannon S. Glaser, Gene Le Sage, Franco Folli, Eugenio Gaudio

Research output: Contribution to journalArticlepeer-review

136 Scopus citations

Abstract

Background & Aims: We investigated the expression of estrogen receptor (ER) α and β subtypes in cholangiocytes of normal and bile duct-ligated (BDL) rats and evaluated the role and mechanisms of estrogens in the modulation of cholangiocyte proliferation. Methods: ER-α and ER-β were analyzed by immunohistochemistry, reverse-transcription polymerase chain reaction, and Western blotting in normal and BDL rats. The effects of the ER antagonists tamoxifen and ICI 182, 780 on cholangiocyte proliferation were evaluated. Results: Cholangiocytes expressed both ER-α and ER-β subtypes, whereas hepatocytes expressed only ER-α. In association with a marked cholangiocyte proliferation and with enhanced estradiol serum levels, the immunoreactivity for ER-α involved a 3-fold higher percentage of cholangiocytes in 3-week BDL than in normal rats; immunore-activity for ER-β showed a 30-fold increase. Western blot analysis showed that during BDL, the total amount of ER-β in cholangiocytes was markedly increased (5-fold), whereas that of ER-α decreased slightly (-25%). Treatment with tamoxifen or ICI 182, 780 of 3-week BDL rats inhibited cholangiocyte proliferation and induced over-expression of Fas antigen and apoptosis in cholangiocytes. In vitro, 17β estradiol stimulated proliferation of cholangiocyte, an effect blocked to the same extent by tamoxifen or ICI 182, 780. Conclusions: This study suggests that estrogens and their receptors play a role in the modulation of cholangiocyte proliferation.

Original languageEnglish (US)
Pages (from-to)1681-1691
Number of pages11
JournalGastroenterology
Volume119
Issue number6
DOIs
StatePublished - Jan 1 2000

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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