THYROXINE ACCELERATES PROLIFERATION OF INJURED LIVER

Background/Aims: Long-term gene transfer into hepatocytes requires DNA synthesis. Although this can be achieved in vitro, using various hepa tic mitogens, marked proliferative response is not seen in vivo in the quiescent liver. We have speculated that controlled reversible liver damage might change the steady state of the liver, and thus render it susceptible to manipulations by growth factors and cytokines, Therefor e, the influence of thyroxine on proliferation of hepatocytes and of b ile duct epithelial cells was investigated, using an in vivo model of thioacetamide-induced liver insult. Methods: Five groups of ten rats e ach were studied: normal rats, thioacetamide-treated, thyroxine-treate d, both thioacetamide and thyroxine-treated, and a 70% partial hepatec tomy group. DNA synthesis was looked at by PCNA labeling. Results: The PCNA labeling indexes of hepatocytes and of bile duct epithelial cell s in rats treated with both thioacetamide and thyroxine (9.5+/-1.2 and 33.8+/-5.7% respectively) were significantly (p<0.0002) higher than t hose of the normal (0.84+/-0.2 and 4.4+/-0.5%), thioacetamide-treated (2.1+/-0.3 and 7.1+/-2.3%) and thyroxine-treated animals (0.6+/-0.3 an d 11+/-5.6%). The labeling index in the hepatectomized animals was sig nificantly higher for hepatocytes (18.3+/-1.2%, p<0.003), but lower fo r biliary cells (15+/-2.6, p<0.05) than that observed in thioacetamide and thyrosine-treated rats. Hypothyroid rats had significantly lower PCNA labeling index, as compared to the thioacetamide-thyroxine-treate d group or the partial hepatectomy group. Conclusions: Following contr olled liver damage, thyroxine is a potent mitogen for both hepatocytes and bile duct epithelial cells,