Exogenous thyroid hormone induces liver enlargement, whilst maintaining regenerative potential--a study relevant to donor preconditioning.
We have investigated thyroid hormone- (T3) induced liver cell hyperplasia in rats to explore the potential utility of primary mitogens within the clinical context of donor conditioning prior to living-related transplantation. A single injection of T3 induced a semi-synchronized proliferative response in hepatocytes, resulting at 10 days in a peak increase in liver mass, liver/body mass ratio, total DNA and total protein. Importantly, the hyperplastic liver induced by T3 exhibits a commensurate increase in metabolic capacity, as assessed by enhanced galactose elimination capacity. Furthermore, when the liver mass had been increased by an injection of T3 given 10 days previously and 70% partial hepatectomy performed, there was a larger remnant liver mass, liver/body mass ratio, total DNA and total protein content 24 h after surgery, compared with animals given a control injection. Interestingly, the regenerative response to surgery was the same in both groups, indicating that prior T3 conditioning did not impair the regenerative response of the liver. Using more stringent conditions to test hepatic functional reserve, following 90% hepatectomy, there was a greater (57%) survival in animals pre-treated with T3 compared to 14% in controls.
Centre for Hepatology, Department of Medicine, Royal Free Campus, Royal Free and University College Medical School, Hampstead, London NW3 2PF, UK. r.malik@rfc.ucl.ac.uk
Raza
R
Malik
Mohammed
M
Habib
Rosemary
R
Tootle
Humphrey
H
Hodgson
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005690:Galactose / Q000378:metabolism; D006498:Hepatectomy; D022781:Hepatocytes / Q000637:transplantation; D006529:Hepatomegaly / Q000139:chemically induced*; D008115:Liver Regeneration / Q000187:drug effects*; D016031:Liver Transplantation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015996:Survival Rate; D014019:Tissue Donors; D019172:Transplantation Conditioning; D014284:Triiodothyronine / Q000494:pharmacology*
D014284:Triiodothyronine; D005690:Galactose