Recent advances in pathophysiology of biliary tree: influence of sex hormones in cholangiocyte growth

Cholangiocytes are epithelial cells that line the biliary tree (1). The intrahepatic biliary tree is characterized by interconnected ducts which starts with canals of Hering, continues into intrahepatic ducts of increasing diameter to end at the level of the extrahepatic bile ducts (2). These cells play a key role in the ductal secretion of water and bicarbonate during the process of bile formation. These cells are also the target in several chronic cholestatic liver diseases (termed cholangiopathies), including primary sclerosing cholangitis (PSC), primary biliary cirrhosis (PBC), polycystic liver disease (PCLD) and cholangiocarcinoma (CCA) (3, 4). During these conditions, the balance between proliferation/loss of cholangiocytes is lost with critical effect on the maintenance of biliary functions and intrahepatic bile ductal mass (3, 5, 6). A typical feature that occurs under specific experimental conditions, such as common bile duct ligation (BDL) (Fig.1). After BDL, there is biliary hyperplasia and secretin stimulated choleresis (a functional marker of cholangiocyte growth) (5). Cholangiocyte growth/apoptosis is regulated by several factors, including growth factors, cytokines, gastrointestinal and sex hormones, such as estrogens, prolactin, follicle-stimulating hormone (FSH), testosterone and progesterone (3, 7, 8, 9). The purpose of this review is to summarize the recent findings on the effects of sex hormones in cholangiocyte pathophysiology. To clarify the mechanisms of action of these substances will provide new potential strategies for the management of chronic liver diseases.