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Review
. 2006 Jun 14;12(22):3537-45.
doi: 10.3748/wjg.v12.i22.3537.

Estrogens and the pathophysiology of the biliary tree

Domenico Alvaro  1 , Maria Grazia Mancino, Paolo Onori, Antonio Franchitto, Gianfranco Alpini, Heather Francis, Shannon Glaser, Eugenio Gaudio
Affiliations
Review

Estrogens and the pathophysiology of the biliary tree

Domenico Alvaro et al. World J Gastroenterol. .

Abstract

The scientific framework concerning estrogen effects on different tissues has expanded enormously during the last decades, when estrogen receptor (ER) subtypes were identified. Estrogens are not only essential for the female reproductive system, but they also control fundamental functions in other tissues including the cardiovascular system, bone, brain and liver. Recently, estrogens have been shown to target the biliary tree, where they modulate the proliferative and secretory activities of cholangiocytes, the epithelial cells lining bile ducts. By acting on both estrogen receptors (ER-alpha) and (ER-beta) subtypes, and by activating either genomic or non-genomic pathways, estrogens play a key role in the complex loop of growth factors and cytokines, which modulates the proliferative response of cholangiocytes to damage. Specifically, estrogens activate intracellular signalling cascades [ERK(1/2) (extracellular regulated kinases (1/2), PI3- kinase/AKT (phosphatidylinositol-3' kinase/AKT)] typical of growth factors such as insulin like growth factor (IGF1), nerve growth factor (NGF) and vascular endothelial growth factor (VEGF), thus potentiating their action. In addition, estrogens stimulate the secretion of different growth factors in proliferating cholangiocytes. This review specifically deals with the recent advances related to the role and mechanisms by which estrogens modulate cholangiocyte functions in normal and pathological conditions.

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Figures

Figure 1
Figure 1
Additive effect of estrogens (EE) and insulin like growth factor-1 (IGF1) in the modulation of cholangiocyte proliferation. EE and IGF1 play additive effects on cholangiocyte proliferation by acting at both receptor and post-receptor levels IGF1 and EE induce, in cholangiocytes, additive increase of phosphorylated ERK1/2.
Figure 2
Figure 2
Immunohistochemistry of ER-α and ER-β in cholangiocytes in different human pathologies, bP < 0.01 , dP < 0.01 vs other columns.
Figure 3
Figure 3
Immunohistochemistry for ER-α and ER-β. Biopsies of human primary biliary cirrhosis showing an intense positivity for both ER-α and ER-β in the proliferating bile ducts. Orig. magn., x 20.
Figure 4
Figure 4
Immunohistochemistry for ER-α and ER-β. Biopsies of human cholangiocarcinoma showing an intense positivity for both ER-α and ER-β. Orig. magn., x 20.
See this image and copyright information in PMC

References

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