title: Prolactin stimulates the proliferation of normal female cholangiocytes by differential regulation of Ca2+-dependent PKC isoforms.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gastroenterology, Università Politecnica delle Marche, Nuovo Polo Didattico, III piano, Ancona, Italy. taffetanisilvia@yahoo.it <taffetanisilvia@yahoo.it>
authors.forename: Silvia
authors.initials: S
authors.lastname: Taffetani
authors.forename: Shannon
authors.initials: S
authors.lastname: Glaser
authors.forename: Heather
authors.initials: H
authors.lastname: Francis
authors.forename: Sharon
authors.initials: S
authors.lastname: DeMorrow
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ueno
authors.forename: Domenico
authors.initials: D
authors.lastname: Alvaro
authors.forename: Luca
authors.initials: L
authors.lastname: Marucci
authors.forename: Marco
authors.initials: M
authors.lastname: Marzioni
authors.forename: Giammarco
authors.initials: G
authors.lastname: Fava
authors.forename: Julie
authors.initials: J
authors.lastname: Venter
authors.forename: Shelley
authors.initials: S
authors.lastname: Vaculin
authors.forename: Bradley
authors.initials: B
authors.lastname: Vaculin
authors.forename: Ian Pak-Yan
authors.initials: IP
authors.lastname: Lam
authors.forename: Vien Hoi-Yi
authors.initials: VH
authors.lastname: Lee
authors.forename: Eugenio
authors.initials: E
authors.lastname: Gaudio
authors.forename: Guido
authors.initials: G
authors.lastname: Carpino
authors.forename: Antonio
authors.initials: A
authors.lastname: Benedetti
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Alpini
mesh_terms: D000818:Animals; D001652:Bile Ducts / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D010766:Phosphorylation; D011388:Prolactin / Q000378:metabolism* / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011981:Receptors, Prolactin / Q000096:biosynthesis
chemical_list: D007527:Isoenzymes; D011981:Receptors, Prolactin; D011388:Prolactin; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha