Temporal pole responds to subtle changes in local thyroid hormone signaling

<p>To study thyroid hormone (TH) signaling in the human brain, we analyzed published microarray data sets of the temporal pole (Brodmann area 38) of 19 deceased donors. An index of TH signaling built on the expression of 19 well known TH-responsive genes in mouse brains (<b>T3S+</b>) varied from 0.92 to 1.1. After Factor analysis, <b>T3S</b><b>+</b> correlated independently with the expression of TH transporters (MCT8, LAT2), TH receptor (TR) beta and TR coregulators (CARM1, MED1, KAT2B, SRC2, SRC3, NCOR2a). Unexpectedly, no correlation was found between <b>T3S+</b> <i>vs</i> DIO2, DIO3, SRC1 or TRα. An unbiased systematic analysis of the entire transcriptome identified a set of 1,649 genes (set #1) with strong positive correlation with <b>T3S+</b> (r&gt;0.75). Factor analysis of set #1 identified two sets of genes that correlated independently with <b>T3S+</b>, sets #2 (329 genes) and #3 (191 genes). When processed through the Molecular Signatures Data Base (MSigDB), both sets #2-3 were enriched with GO-sets related to synaptic transmission and metabolic processes. Ranking individual human brain donors according to their <b>T3S+</b> led us to identify 1,262 genes (set #4) with &gt;1.3-fold higher expression in the top half. The analysis of the overlapped genes between sets #1 and #4 resulted in 769 genes (set #5), which have a very similar MSigDB signature as sets #2-3. In conclusion, gene expression in the human temporal pole can be assessed through <b>T3S+</b> and fluctuates with subtle variations in local TH signaling.</p>