Steroid receptors are pleiotropic transcription factors that coordinate
adaptation to different physiological states. An important
target organ is the brain, but even though
their effects are well studied in specific regions, brain-wide steroid
targets and mediators remain largely
unknown due to the complexity of the brain. Here, we tested the idea
that novel aspects
of steroid action can be identified
through spatial correlation of steroid receptors with genome-wide mRNA
different regions in the mouse brain.
First, we observed significant coexpression of six nuclear receptors
receptor (Ar), estrogen receptor alpha (Esr1), estrogen receptor beta (Esr2), glucocorticoid receptor (Gr), mineralocorticoid receptor (Mr), and progesterone receptor (Pgr)]
with sets of steroid target genes that were identified in single brain
regions. These coexpression relationships were also
present in distinct other brain regions,
suggestive of as yet unidentified coordinate regulation of brain regions
example, glucocorticoids and estrogens.
Second, coexpression of a set of 62 known NR coregulators and the six
in 12 nonoverlapping mouse brain regions
revealed selective downstream pathways, such as Pak6 as a mediator for the effects of Ar and Gr on dopaminergic transmission. Third, Magel2 and Irs4
were identified and validated as strongly responsive targets to the
estrogen diethylstilbestrol in the mouse hypothalamus.
The brain- and genome-wide correlations of
mRNA expression levels of six steroid receptors that we provide
constitute a rich
resource for further predictions and
understanding of brain modulation by steroid hormones.
- nuclear receptors
- transcription regulation