Vasopressin stimulates DNA synthesis in cultured rat hepatocytes.
Liver regeneration following partial hepatectomy is significantly impaired in rats with hereditary vasopressin (AVP) deficiency. This suggested that AVP might have a direct effect on cultured rat hepatocytes. Hepatocytes from male Sprague-Dawley rats were isolated using a two-step collagenase perfusion technique and plated at a density of 10(5)/16-mm Primaria plate. After a suitable attachment period, hepatocytes were incubated with minimal essential media, AVP, AVP plus a specific AVP antagonist, or oxytocin. Hepatocyte proliferation was measured by [3H]thymidine incorporation ([3H]Thy) into hepatocyte DNA. AVP (10 nM) increased [3H]Thy significantly (and this effect was blocked by an AVP-specific antagonist (50 nM). Oxytocin had no effect on hepatocyte DNA synthesis. To further investigate the influence of AVP on hepatocyte proliferation, the effect of AVP on transforming growth factor-alpha (TGF-alpha)-stimulated hepatocyte proliferation was also studied. This combination was chosen based on the ability of AVP to inhibit the biologic effects of EGF (a TGF-alpha analog). There was significant attenuation of TGF-alpha (50 nM)-stimulated [3H]Thy in the presence of AVP (10 nM). In summary: (1) AVP stimulates proliferation of cultured rat hepatocytes. (2) The effect of AVP can be significantly abolished by a specific AVP antagonist. (3) The proliferative response of AVP is specific. (4) AVP significantly attenuates TGF-alpha-stimulated hepatocyte hepatic DNA synthesis. Further studies should elucidate the mechanisms for the effects of AVP on hepatic proliferation alone or in combination with other factors.
Bhora
F Y
FY
Department of Surgery, University of Michigan Medical School, Ann Arbor 48109.
Kothary
P C
PC
Imanishi
H
H
Eckhauser
F E
FE
Raper
S E
SE
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008099:Liver / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D010121:Oxytocin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013936:Thymidine / Q000378:metabolism; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D014316:Tritium
D016211:Transforming Growth Factor alpha; D014316:Tritium; D001127:Arginine Vasopressin; D010121:Oxytocin; D004247:DNA; D013936:Thymidine