Figure 4.

C57BL/6 mice were divided into two groups – one given a single acute T3 injection (red arrow) and another group given multiple T3 injections intraperitoneally over 14 days (violet arrows). Microarrays on liver tissue to study gene expression patterns were done 6 h after acute and chronic T3 injections. Certain target genes responded acutely with a brief increase in mRNA expression, which subsequently became desensitized to T3 and declined (e.g., Bcl3, Thrsp) (red line). There were also target genes positively regulated only by chronic T3 exposure, but initially unresponsive to T3 (e.g., Fgf21, Cyp17a1) (violet line). A third group of genes were positively regulated by both acute and chronic T3 exposure (e.g., Dio1, Fndc5, Idh3a) (green line). Different histone modifications influence differential temporal expression patterns during the development of thyrotoxicosis, with H3 acetylation regulating acute T3 responses and H3K4 trimethylation regulating chronic T3 stimulation (21).