TI - Prolactin stimulates the proliferation of normal female cholangiocytes by differential regulation of Ca2+ -dependent PKC isoforms . AB - Background Prolactin promotes proliferation of several cells . Prolactin receptor exists as two isoforms : long and short , which activate different transduction pathways including the Ca2+ -dependent PKC -signaling . No information exists on the role of prolactin in the regulation of the growth of female cholangiocytes . The rationale for using cholangiocytes from female rats is based on the fact that women are preferentially affected by specific cholangiopathies including primary biliary cirrhosis . We propose to evaluate the role and mechanisms of action by which prolactin regulates the growth of female cholangiocytes . Results Normal cholangiocytes express both isoforms (long and short) of prolactin receptors , whose expression increased following BDL . The administration of prolactin to normal female rats increased cholangiocyte proliferation . In purified normal female cholangiocytes , prolactin stimulated cholangiocyte proliferation , which was associated with increased [Ca2+] i levels and PKCbeta-I phosphorylaTION but decreased PKCalpha PHOSphorylation . Administration of an anti-prolactin antibody to BDL female rats decreased cholangiocyte proliferation . Normal female cholangiocytes express and secrete prolactin , which was increased in BDL rats . The data show that prolactin stimulates normal cholangiocyte growth by an autocrine mechanism involving phosphorylaTION of PKCbeta-I and dePHOSphorylation of PKCalpha . Conclusion We suggest that in female rats : (i) prolactin has a trophic effect on the growth of normal cholangiocytes by phosphorylaTION of PKCbeta-I and dePHOSphorylation of PKCalpha ; and ( iii ) cholangiocytes express and secrete prolactin , which by an autocrine mechanism participate in regulation of cholangiocyte proliferation . Prolactin may be an important therapeutic approach for the management of cholangiopathies affecting female patients .