Microarray analysis of mitogenic effects of T3 on the rat liver.
OBJECTIVE
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.
Bungay
Anton
A
Royal Free & University College Medical School, Rowland Hill Street, London.
Selden
Clare
C
Brown
David
D
Malik
Raza
R
Hubank
Mike
M
Hodgson
Humphrey
H
D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics; D004261:DNA Replication; D030541:Databases, Genetic; D020869:Gene Expression Profiling / Q000379:methods*; D006133:Growth Substances / Q000008:administration & dosage / Q000378:metabolism*; D007279:Injections, Subcutaneous; D008099:Liver / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014284:Triiodothyronine / Q000008:administration & dosage / Q000378:metabolism*; D000097642:GADD45 Proteins
D000943:Antigens, Differentiation; D019938:Cyclin D1; D006133:Growth Substances; D012313:RNA; D014284:Triiodothyronine; C530106:Ccnd1 protein, rat; C508094:Gadd45b protein, rat; D000097642:GADD45 Proteins