Inhibition of DNA synthesis by somatostatin in rat hepatocytes stimulated by hepatocyte growth factor or epidermal growth factor.
The antiproliferative effects of somatostatin on hepatocytes stimulated by hepatocyte growth factor (HGF) or epidermal growth factor (EGF) were investigated using primary cultures of adult rat hepatocytes. Somatostatin inhibits HGF-induced (at a dose of 10 ng/mL) or EGF-induced (at a dose of 100 ng/mL) 3H-thymidine incorporation into hepatocytes in a dose-dependent manner (10(-10) to 10(-8) M). This inhibition was confirmed by autoradiography. The effect of somatostatin was nontoxic as judged by preserved albumin synthesis, a marker for differentiated hepatocyte function. In the presence or absence of somatostatin, neither HGF nor EGF significantly altered intracellular cyclic adenosine monophosphate (cAMP). We conclude that somatostatin is a potent inhibitor of HGF- or EGF-induced deoxyribonucleic acid synthesis in adult rat hepatocytes. The mechanism of this inhibition appears to be independent of cAMP. The significance of somatostatin in liver regeneration has yet to be assessed.
Department of Surgery, University of Michigan Medical Center, Ann Arbor.
N
N
Kokudo
P C
PC
Kothary
F E
FE
Eckhauser
T
T
Nakamura
S E
SE
Raper
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology; D004247:DNA / Q000096:biosynthesis*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D006133:Growth Substances / Q000494:pharmacology*; D017228:Hepatocyte Growth Factor; D015151:Immunoblotting; D008099:Liver / Q000166:cytology; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000502:physiology*
D006133:Growth Substances; D013004:Somatostatin; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor; D004247:DNA; D000242:Cyclic AMP