Novel functional hepatocyte cell line derived from spontaneous dwarf rat: model of growth hormone function in vitro

Hum Cell. 2010 Nov;23(4):164-72. doi: 10.1111/j.1749-0774.2010.00097.x.

Abstract

Currently there is no good hepatocyte model for studying growth hormone (GH) function that reflects its normal physiological roles. Here we report the establishment of a functional hepatocyte cell line, SDRL-1, from the liver of young male spontaneous dwarf rats (SDR), with isolated GH deficiency. This line has been maintained in Dulbecco's Modified Eagle Medium (DMEM)/F12 medium supplemented with 10% fetal bovine serum (FBS) with retention of a near diploid karyotype for extended periods of time. When grown as a monolayer sheet, it displayed a pavement-like appearance and contact inhibition. These cells have a poorly developed rough endoplasmic reticulum (r-ER), few mitochondria and glycogen granules, and produce a small amount of albumin and α-fetoprotein, that is enhanced when grown on a collagen gel sponge. Human recombinant GH stimulated JAK2 and STAT5b tyrosine phosphorylation and IGF-I production in a concentration-dependent manner. When the cells were cultured with GH-supplemented medium, the number of mitochondria and glycogen granules increased together with the r-ER and Golgi apparatus. A number of microvilli were observed on the surface of the cultured cells, further suggesting that this cell line is composed of normally functioning hepatocytes. In summary, we established a novel hepatocyte cell line (SDRL-1), that appears to display normal function, which we propose can serve as a good in vitro model for studying GH-target organ interactions.

MeSH terms

  • Albumins / biosynthesis
  • Animals
  • Cell Line
  • Dose-Response Relationship, Drug
  • Dwarfism, Pituitary
  • Endoplasmic Reticulum, Rough
  • Glucose / biosynthesis
  • Glycogen / biosynthesis
  • Golgi Apparatus
  • Growth Hormone / pharmacology*
  • Growth Hormone / physiology*
  • Hepatocytes* / metabolism
  • Hepatocytes* / ultrastructure
  • Insulin-Like Growth Factor I / metabolism
  • Janus Kinase 2 / metabolism
  • Mitochondria
  • Phosphorylation
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Somatotropin / metabolism
  • STAT5 Transcription Factor / metabolism
  • Urea / metabolism
  • alpha-Fetoproteins / biosynthesis

Substances

  • Albumins
  • Receptors, Somatotropin
  • STAT5 Transcription Factor
  • Stat5b protein, rat
  • alpha-Fetoproteins
  • Insulin-Like Growth Factor I
  • Urea
  • Growth Hormone
  • Glycogen
  • Jak2 protein, rat
  • Janus Kinase 2
  • Glucose