Possible roles of insulin-like growth factor in regulation of physiological and pathophysiological liver growth.
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.
Skrtic
S
S
Research Center for Endocrinology and Metabolism (RCEM), Sahlgrenska University Hospital, Göteborg, Sweden.
Wallenius
K
K
Sjögren
K
K
Isaksson
O G
OG
Ohlsson
C
C
Jansson
J O
JO
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*
D017077:Culture Media, Conditioned; D008934:Mitogens; D013002:Somatomedins; D017228:Hepatocyte Growth Factor; D004247:DNA