Triiodothyronine enhances the regenerative capacity of the liver following partial hepatectomy.
This study investigates the effects of administering a primary mitogen, triiodothyronine (T(3)), at the time of 70% partial hepatectomy (PH) in the rat, thus combining the 2 distinct pathways of liver growth: direct hyperplasia and compensatory regeneration. T(3) enhances the proliferative response of hepatocytes within the liver following PH. Flash bromodeoxyuridine (BrdU) labeling showed a cell proliferation index 24 hours after PH alone of 26.5% +/- 2.8%; when T(3) was administered at PH, it increased to 39.5% +/- 5.0% (P <.01 compared with PH alone). Continuous BrdU labeling performed every 6 hours between 15 and 72 hours following surgery showed an index of 84.0% +/- 4.0% when T(3) was administered at PH compared with 71.0% +/- 4.0% with PH alone (P <.01 compared with PH alone). This increase in cell proliferation resulted in a larger liver mass at 4 days in rats receiving T(3) at PH compared with PH alone (P <.05 compared with PH alone). The difference in liver mass was matched with corresponding increases in total DNA and total protein levels as well as cell division, as confirmed by the frequent demonstration of twin daughter cells on histology. In conclusion, this study shows that a single dose of T(3) enhances the regenerative capacity of the liver following PH. The ability to enhance cell proliferation during compensatory hyperplasia following PH could be therapeutically valuable if applicable to humans.
Malik
Raza
R
Centre for Hepatology, Department of Medicine, Royal Free Campus, Royal Free and University College Medical School, Hampstead, London, England. r.malik@rfc.ucl.ac.uk
Mellor
Neil
N
Selden
Clare
C
Hodgson
Humphrey
H
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001663:Bilirubin / Q000097:blood; D001973:Bromodeoxyuridine; D002455:Cell Division / Q000187:drug effects; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology; D006863:Hydrogen-Ion Concentration; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D008934:Mitogens / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016196:S Phase / Q000187:drug effects; D014284:Triiodothyronine / Q000494:pharmacology*
D008934:Mitogens; D014284:Triiodothyronine; D000410:Alanine Transaminase; D001973:Bromodeoxyuridine; D001663:Bilirubin