title: Role of follicle-stimulating hormone on biliary cyst growth in autosomal dominant polycystic kidney disease.
abstract: BACKGROUND
  Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder characterized by the progressive development of renal and hepatic cysts. Follicle-stimulating hormone (FSH) has been demonstrated to be a trophic factor for biliary cells in normal rats and experimental cholestasis induced by bile duct ligation (BDL).
  
  
  OBJECTIVE
  To assess the effect of FSH on cholangiocyte proliferation during ADPKD using both in vivo and in vitro models.
  
  
  METHODS
  Evaluation of FSH receptor (FSHR), FSH, phospho-extracellular-regulated kinase (pERK) and c-myc expression in liver fragments from normal patients and patients with ADPKD. In vitro, we studied proliferating cell nuclear antigen (PCNA) and cAMP levels in a human immortalized, non-malignant cholangiocyte cell line (H69) and in an immortalized cell line obtained from the epithelium lining the hepatic cysts from the patients with ADPKD (LCDE) with or without transient silencing of the FSH gene.
  
  
  RESULTS
  Follicle-stimulating hormone is linked to the active proliferation of the cystic wall and to the localization of p-ERK and c-myc. This hormone sustains the biliary growth by activation of the cAMP/ERK signalling pathway.
  
  
  CONCLUSIONS
  These results showed that FSH has an important function in cystic growth acting on the cAMP pathway, demonstrating that it provides a target for medical therapy of hepatic cysts during ADPKD.
authors.affiliation: Department of Anatomical, Histological, Forensic Medicine and Orthopedic Sciences, University of Rome Sapienza, Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Onori
authors.forename: Romina
authors.initials: R
authors.lastname: Mancinelli
authors.forename: Antonio
authors.initials: A
authors.lastname: Franchitto
authors.forename: Guido
authors.initials: G
authors.lastname: Carpino
authors.forename: Anastasia
authors.initials: A
authors.lastname: Renzi
authors.forename: Stefania
authors.initials: S
authors.lastname: Brozzetti
authors.forename: Julie
authors.initials: J
authors.lastname: Venter
authors.forename: Heather
authors.initials: H
authors.lastname: Francis
authors.forename: Shannon
authors.initials: S
authors.lastname: Glaser
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Jefferson
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Alpini
authors.forename: Eugenio
authors.initials: E
authors.lastname: Gaudio
mesh_terms: D000368:Aged; D000818:Animals; D016022:Case-Control Studies; D002460:Cell Line; D049109:Cell Proliferation; D015529:Choledochal Cyst / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000242:Cyclic AMP / Q000378:metabolism; D003560:Cysts / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D043373:Follicle Stimulating Hormone, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008107:Liver Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D034622:RNA Interference; D011962:Receptors, FSH / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection
chemical_list: D043373:Follicle Stimulating Hormone, Human; C489427:MYC protein, human; D018809:Proliferating Cell Nuclear Antigen; D016271:Proto-Oncogene Proteins c-myc; D011962:Receptors, FSH; D000242:Cyclic AMP; D048049:Extracellular Signal-Regulated MAP Kinases