title: Dose-specific or dose-dependent effect of growth hormone treatment on the proliferation and differentiation of cultured neuronal cells.
abstract: OBJECTIVE
  GH controls the proliferation of cartilage, fibroblasts or the differentiation of adipose and muscle tissue. However, the effect of GH on neuronal cells remains unknown. The present study was conducted to determine the proliferative or differentiating effect of GH on the nervous system in vitro.
  
  
  METHODS
  Neuronal hybrid cells (VSC4.1) were cultured with GH. The concentration ranged from 0.134 microg/ml up to 1.34 mg/ml. A cell confluency and MTT assay, cell cycle phase analysis with flow cytometry, extracellular receptor kinase (ERK) phosphorylation and mitogen activated protein kinase (MAPK) inhibitor (PD98050) assays were all performed to determine the effect on proliferation. Differentiation was evaluated by neurite outgrowth and neurofilament expression. Terminally differentiated neurons were stained by Hoechst 33342 for apoptotic nuclear fragmentation by degeneration. Poly-adenosyl ribose polymerase (PARP) expression and its cleavage products were evaluated.
  
  
  RESULTS
  Cells at concentrations between 0.134 microg/ml and 1.34 microg/ml of GH proliferated with ERK phosphorylation, which was attenuated by MAPK inhibitors. Proliferation decreased at concentrations higher than 13.4 microg/ml; however, neurite outgrowth was observed at these concentrations. Terminally differentiated cells underwent apoptosis and showed nuclear fragmentation by Hoechst 33342 staining. PARP expression was increased with caspase-3 dependent-cleaved fragment.
  
  
  CONCLUSIONS
  Our in vitro data demonstrate that GH exerts dual effects; proliferation with a specific GH dose window, or differentiation in a dose-dependent manner in cultured neuronal hybrid cells.
authors.affiliation: Department of Preventive Medicine, Seoul National University, Esther Clinic, Seoul 110-744, Republic of Korea.
authors.forename: Esther
authors.initials: E
authors.lastname: Lyuh
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Manho
authors.initials: M
authors.lastname: Kim
authors.forename: Jung-Kwon
authors.initials: JK
authors.lastname: Lee
authors.forename: Kyong-Soo
authors.initials: KS
authors.lastname: Park
authors.forename: Keun-Young
authors.initials: KY
authors.lastname: Yoo
authors.forename: Kwang-Woo
authors.initials: KW
authors.lastname: Lee
authors.forename: Yoon-Ok
authors.initials: YO
authors.lastname: Ahn
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D013006:Growth Hormone / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D051381:Rats
chemical_list: D013006:Growth Hormone