title: Possible roles of insulin-like growth factor in regulation of physiological and pathophysiological liver growth.
abstract: OBJECTIVE
  Almost all circulating insulin-like growth factor-1 (IGF-1) is produced and secreted from the liver. However, the possible role of IGF-1 in local regulation of liver functions including liver growth is unclear. In the present study, we investigated the role of IGF-1 on liver growth in vivo and in hepatic stellate cell function in vitro.
  
  
  RESULTS
  Liver-specific knock-out of the IGF-1 gene by use of the cre-loxP system caused enhanced liver growth, possibly reflecting increased growth hormone (GH) secretion due to decreased negative feedback by IGF-1. Studies on cultured rat hepatic stellate cells (HSC) showed that IGF-1 and hepatocyte-conditioned medium (PCcM) time- and dose-dependently increased hepatocyte growth factor (HGF) mRNA and HGF immunoreactivity. IGF-1 and PCcM also enhanced DNA synthesis in the HSC cultures. The PCcM did not contain bioactive IGF-1 and was also able to stimulate proliferation when prepared under serum- and hormone-free conditions.
  
  
  CONCLUSIONS
  In vivo results show that IGF-1 is not essential for normal growth of the intact liver. The in vitro results indicate that both IGF-1 and IGF- 1-independent factor(s) from hepatocytes can stimulate HGF production by HSC. It remains to be investigated whether these effects are of importance for liver regeneration or pathological conditions.
authors.affiliation: Research Center for Endocrinology and Metabolism (RCEM), Sahlgrenska University Hospital, Göteborg, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Skrtic
authors.forename: K
authors.initials: K
authors.lastname: Wallenius
authors.forename: K
authors.initials: K
authors.lastname: Sjögren
authors.forename: O G
authors.initials: OG
authors.lastname: Isaksson
authors.forename: C
authors.initials: C
authors.lastname: Ohlsson
authors.forename: J O
authors.initials: JO
authors.lastname: Jansson
mesh_terms: D000818:Animals; D002455:Cell Division / Q000502:physiology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis / Q000235:genetics; D022781:Hepatocytes / Q000166:cytology / Q000473:pathology; D008099:Liver / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D008934:Mitogens / Q000494:pharmacology; D013002:Somatomedins / Q000172:deficiency / Q000502:physiology*
chemical_list: D017077:Culture Media, Conditioned; D008934:Mitogens; D013002:Somatomedins; D017228:Hepatocyte Growth Factor; D004247:DNA