Thyroxine accelerates proliferation of injured liver cells.
OBJECTIVE
Long-term gene transfer into hepatocytes requires DNA synthesis. Although this can be achieved in vitro, using various hepatic 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. Therefore, the influence of thyroxine on proliferation of hepatocytes and of bile duct epithelial cells was investigated, using an in vivo model of thioacetamide-induced liver insult.


METHODS
Five groups of ten rats each were studied: normal rats, thioacetamide-treated, thyroxine-treated, both thioacetamide and thyroxine-treated, and a 70% partial hepatectomy group. DNA synthesis was looked at by PCNA labeling.


RESULTS
The PCNA labeling indexes of hepatocytes and of bile duct epithelial cells 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 those of the normal (0.84+/-0.2 and 4.4+/-0.50%), thioacetamide-treated (2.1+/-0.3 and 7.1+/-2.3%) and thyroxine-treated animals (0.6+/-0.3 and 11+/-5.6%). The labeling index in the hepatectomized animals was significantly higher for hepatocytes (18.3+/-1.2%, p<0.003), but lower for biliary cells (15+/-2.6, p<0.05) than that observed in thioacetamide and thyroxine-treated rats. Hypothyroid rats had significantly lower PCNA labeling index, as compared to the thioacetamide-thyroxine-treated group or the partial hepatectomy group.


CONCLUSIONS
Following controlled liver damage, thyroxine is a potent mitogen for both hepatocytes and bile duct epithelial cells.
Oren
R
R
Department of Gastroenterology, Tel-Aviv Sourasky Medical Center, Israel.
Resnick
M B
MB
Brill
S
S
Dotan
I
I
Zaidel
L
L
Lifshits-Mercer
B
B
Halpern
Z
Z
D000818:Animals; D001652:Bile Ducts / Q000166:cytology; D002455:Cell Division / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects; D005260:Female; D015316:Genetic Therapy; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013974:Thyroxine / Q000494:pharmacology*
D018809:Proliferating Cell Nuclear Antigen; D013974:Thyroxine