Role of follicle-stimulating hormone on biliary cyst growth in autosomal dominant polycystic kidney disease

Liver Int. 2013 Jul;33(6):914-25. doi: 10.1111/liv.12177. Epub 2013 Apr 25.

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).

Aims: 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.

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Case-Control Studies
  • Cell Line
  • Cell Proliferation*
  • Choledochal Cyst / genetics
  • Choledochal Cyst / metabolism*
  • Choledochal Cyst / pathology
  • Cyclic AMP / metabolism
  • Cysts / genetics
  • Cysts / metabolism*
  • Cysts / pathology
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Female
  • Follicle Stimulating Hormone, Human / genetics
  • Follicle Stimulating Hormone, Human / metabolism*
  • Humans
  • Liver Diseases / genetics
  • Liver Diseases / metabolism*
  • Liver Diseases / pathology
  • Male
  • Middle Aged
  • Phosphorylation
  • Polycystic Kidney, Autosomal Dominant / genetics
  • Polycystic Kidney, Autosomal Dominant / metabolism*
  • Polycystic Kidney, Autosomal Dominant / pathology
  • Proliferating Cell Nuclear Antigen / metabolism
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA Interference
  • Receptors, FSH / metabolism
  • Signal Transduction
  • Transfection

Substances

  • Follicle Stimulating Hormone, Human
  • MYC protein, human
  • Proliferating Cell Nuclear Antigen
  • Proto-Oncogene Proteins c-myc
  • Receptors, FSH
  • Cyclic AMP
  • Extracellular Signal-Regulated MAP Kinases

Supplementary concepts

  • Polycystic liver disease