title: Novel functional hepatocyte cell line derived from spontaneous dwarf rat: model of growth hormone function in vitro.
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.
authors.affiliation: Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Toho University School of Medicine, Tokyo, Japan. m-ishikawa@med.toho-u.ac.jp
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tachibana
authors.forename: Gen
authors.initials: G
authors.lastname: Yoshino
authors.forename: Hisashi
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tanaka
mesh_terms: D000418:Albumins / Q000096:biosynthesis; D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004393:Dwarfism, Pituitary; D018870:Endoplasmic Reticulum, Rough; D005947:Glucose / Q000096:biosynthesis; D006003:Glycogen / Q000096:biosynthesis; D006056:Golgi Apparatus; D013006:Growth Hormone / Q000494:pharmacology* / Q000502:physiology*; D022781:Hepatocytes / Q000378:metabolism / Q000648:ultrastructure; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D053614:Janus Kinase 2 / Q000378:metabolism; D008928:Mitochondria; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011986:Receptors, Somatotropin / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D014508:Urea / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000096:biosynthesis
chemical_list: D000418:Albumins; D011986:Receptors, Somatotropin; D050799:STAT5 Transcription Factor; C494097:Stat5b protein, rat; D000509:alpha-Fetoproteins; D007334:Insulin-Like Growth Factor I; D014508:Urea; D013006:Growth Hormone; D006003:Glycogen; C507927:Jak2 protein, rat; D053614:Janus Kinase 2; D005947:Glucose