title: Alfa and beta estrogen receptors and the biliary tree.
abstract: This manuscript summarizes recent data showing that estrogens and their receptors play an important role in modulating cholangiocyte proliferation. We have recently demonstrated that rat cholangiocytes express both estrogen receptors (ER)-alpha and -beta subtypes, while hepatocytes only express ER-alpha. ER and especially the ER-beta subtype, are overexpressed in cholangiocytes proliferating after bile duct ligation (BDL) in the rat, in association with enlarged bile duct mass and with enhanced estradiol serum levels. Cholangiocyte proliferation, during BDL, is impaired by estrogen antagonists (tamoxifen, ICI 182,780) which furthermore, induce the overexpression of Fas antigen and activate apoptosis of proliferating cholangiocytes. 17beta-estradiol stimulates, in vitro cholangiocyte proliferation, and this effect is individually blocked by tamoxifen or ICI 182,780. Cholangiocyte proliferation during BDL was associated with an enhanced protein expression of phosphorylated extracellular regulated kinases (ERK)1/2 which is, in contrast, negatively modulated by tamoxifen in association with its antiproliferative effect. This indicates a major involvement of the ERK system in the estrogen modulation of cholangiocyte proliferation.
authors.affiliation: Division of Gastroenterology, Department of Clinical Medicine, University of Rome 'La Sapienza', Via valsolda 45/i, 00141 Rome, Italy. alvaro@axrma.uniromal.it
authors.forename: Domenico
authors.initials: D
authors.lastname: Alvaro
authors.forename: G
authors.initials: G
authors.lastname: Alpini
authors.forename: P
authors.initials: P
authors.lastname: Onori
authors.forename: A
authors.initials: A
authors.lastname: Franchitto
authors.forename: S S
authors.initials: SS
authors.lastname: Glaser
authors.forename: G
authors.initials: G
authors.lastname: Le Sage
authors.forename: F
authors.initials: F
authors.lastname: Folli
authors.forename: A F
authors.initials: AF
authors.lastname: Attili
authors.forename: E
authors.initials: E
authors.lastname: Gaudio
mesh_terms: D000818:Animals; D001653:Bile Ducts, Intrahepatic / Q000737:chemistry / Q000166:cytology*; D002455:Cell Division / Q000187:drug effects; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D006801:Humans; D051381:Rats; D011960:Receptors, Estrogen / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011960:Receptors, Estrogen