Exogenous thyroid hormone induces liver enlargement, whilst maintaining regenerative potential - A study relevant to donor preconditioning

We have investigated thyroid hormone- (T(3)) 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 T(3) 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 T(3) 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 T(3) 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 T(3) 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 T(3) compared to 14% in controls.