The Role of the Bcl-3 Proto-Oncogene in Thyroid Hormone-Induced Liver Cell Proliferation

The aim of the study was to determine if thyroid hormone-induced liver cell proliferation occurs through the Bcl-3 proto-oncogene. Rodents (including Bcl-3 knockout mice and the wild-type strain) were injected with a single dose of tri-iodothyronine (T₃) and sacrificed at various time points. Hepatic mRNA (real-time polymerase chain reaction ) and protein expression (Western analysis) of Bcl-3 was quantified in rats stimulated with T₃. Cell proliferation was induced in a variety of cell types after T₃ injection at 24 h including hepatocytes (7 ± 1.1% vs. 0.45 ± 0.025%; P  < 0.01), hepatic nonparenchymal cells (3.8 ± 1.2% vs. 0.3 ± 0.01%; P  < 0.01), renal tubular cells (8.1 ± 1.6% vs. 0.2 ± 0.035%; P  < 0.01), and splenic lymphocytes (4.8 ± 1.2% vs. 0.35 ± 0.02%; P  < 0.01). We showed a twofold increase in hepatic Bcl-3 mRNA ( P  < 0.01) and protein expression ( P  < 0.01) at 24 h in rats stimulated with T₃. However, there were no differences in the rate of liver cell proliferation between Bcl-3 knockout mice and the wild-type strain (0.4 ±  0.15% vs. 0.3 ± 0.1%), indicating that Bcl-3 was not functionally involved in thyroid hormone-induced liver cell proliferation. A single gene is unlikely to initiate the process of thyroid hormone-induced cell proliferation. A complex interaction between the genomic and nongenomic effects of thyroid hormone is likely to regulate the mitogenic effects.