Estrogens maintain bile duct mass and reduce apoptosis after biliodigestive anastomosis in bile duct ligated rats.
OBJECTIVE
Disapperacence of bile ducts (ductopenia) represents the terminal, common stage of human cholangiopathies, and estrogens exert a major role in stimulating cholangiocyte proliferation. We thus evaluated whether estrogen administration protect from the bile duct loss induced by the biliary-digestive diversion in bile duct ligated (BDL) rats.


METHODS
After 3 weeks of BDL, rats were subjected to biliary-digestive diversion and treated with daily injections of 17beta-estradiol or a control solution.


RESULTS
Both after 7 and 14 days from the biliary-digestive diversion a marked increase of the number of apoptotic cholangiocytes was observed. In contrast, 17beta-estradiol significantly reduced cholangiocyte apoptosis. 17beta-estradiol also prevented the biliary-digestive diversion-induced loss of PCNA-positive cholangiocytes and of the bile duct mass. Biliary-digestive diversion determined a marked reduction of ERK1/2 phopsphorylation in cholangiocytes that was reversed by the administration of 17beta-estradiol.


CONCLUSIONS
This study indicates that estrogens prevent the increase of cholangiocyte apoptosis and loss of cholangiocyte proliferation induced by the biliary-digestive diversion in the BDL rat. In parallel, 17beta-estradiol also enhanced ERK1/2 phosphorylation, which is instead strongly reduced by the biliary-digestive diversion. These novel findings suggest that estrogens could prevent the evolution of cholangiopathies toward ductopenia.
Clinica di Gastroenterologia, Università Politecnica delle Marche, INRCA, IRCCS, Via Tronto, Ancona, 60020, Italy. g.svegliati@univpm.it
Gianluca
G
Svegliati-Baroni
Roberto
R
Ghiselli
Marco
M
Marzioni
Domenico
D
Alvaro
Federico
F
Mocchegiani
Stefania
S
Saccomanno
Valerio
V
Sisti
Laura
L
Ugili
Fiorenza
F
Orlando
Gianfranco
G
Alpini
Vittorio
V
Saba
Antonio
A
Benedetti
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001649:Bile Duct Diseases / Q000473:pathology / Q000517:prevention & control*; D001652:Bile Ducts / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D001835:Body Weight; D049109:Cell Proliferation; D004958:Estradiol / Q000008:administration & dosage*; D004967:Estrogens / Q000008:administration & dosage; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000032:analysis; D048052:Mitogen-Activated Protein Kinase 3 / Q000032:analysis; D009929:Organ Size; D010766:Phosphorylation; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D004967:Estrogens; D018809:Proliferating Cell Nuclear Antigen; D004958:Estradiol; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3