Microarray analysis of mitogenic effects of T3 on the rat liver.

BACKGROUND AND AIM: A single dose of the thyroid hormone tri-iodothyronine, T3, can enhance both size and function of normal rodent liver, which is potentially of value in the treatment of liver disease. However the mechanism of this has not been fully elucidated, and it cannot be modeled in vitro. We therefore investigated the transcriptome response to T3 in rat liver in vivo.

METHODS

After adult rats were administered 5 microg T3 subcutaneously, a whole rat genome microarray comparing global hepatic gene expression against vehicle-only treated liver after 3 h was performed.

RESULTS

Informative transcripts which had identifiable gene ontology biological processes were grouped according to function, broadly reflecting general metabolic effects and those linked to cell-proliferation control. We then compared the transcriptome response after 5-microg T3 initiating hepatocyte DNA synthesis (mitogenic) with that after 0.1 microg T3, a supraphysiological amount not initiating hepatocyte DNA synthesis.

CONCLUSIONS

We compared the results with published results of the response to other primary mitogens, and identified the Gadd45beta/MyD118 gene as a common early factor upregulated during proliferation.