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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Estrogen receptors in cholangiocytes and the progression of primary biliary cirrhosis.

BACKGROUND/AIMS: Estrogen receptors (ER) in cholangiocytes of primary biliary cirrhosis ( PBC) patients and their relationship with cell proliferation and death were evaluated. METHODS: Liver biopsies from PBC patients with different histological stages were investigated by immunohistochemistry for ER-alpha and -beta, cytokeratin-19, proliferating cellular nuclear antigen (PCNA), Fas and terminal deoxynucleotide transferase end labelling (TUNEL). Normal livers and livers from primary sclerosing cholangitis and alcoholic cirrhosis were investigated as controls. RESULTS: ER-alpha and -beta were observed in cholangiocytes of PBC patients but not in normal liver. In PBC, positivity for ER-beta was high (50-65 %) in all histological stages while, positivity for ER-alpha increased from 1% in stage I to 12 % in stage III (positivity correlated and co-localized in the same cell with PCNA). In stage IV of PBC, cholangiocytes were negative for ER-alpha in association with a lower PCNA positivity and with maximal degree of ductopenia. ER-alpha positivity in cholangiocytes of PBC patients was markedly lower than primary sclerosing cholangitis and alcoholic cirrhosis. CONCLUSIONS: ER are expressed in PBC and other pathologies associated with cholangiocyte proliferation but not in normal subjects. The low expression of ER-alpha in PBC and their disappearance in the advanced histological stages suggests that an estrogenic deficiency could favour the evolution of this disease toward ductopenia.[1]


  1. Estrogen receptors in cholangiocytes and the progression of primary biliary cirrhosis. Alvaro, D., Invernizzi, P., Onori, P., Franchitto, A., De Santis, A., Crosignani, A., Sferra, R., Ginanni-Corradini, S., Mancino, M.G., Maggioni, M., Attili, A.F., Podda, M., Gaudio, E. J. Hepatol. (2004) [Pubmed]
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