Figure 3.

CLOCK-mediated gene-specific regulation of glucocorticoid action in peripheral target tissues. Circulating cortisol concentrations in humans fluctuate diurnally, as indicated in the top panel. The expression of glucocorticoid-target genes is also expected to fluctuate depending on the changes of circulating cortisol concentrations. However, this diurnal fluctuation of gene expression is suppressed through acetylation of GR by locally expressed CLOCK/BMAL1 heterodimers, possibly functioning as a local counter-regulatory feedback loop to the circulating glucocorticoids. Thus, high levels of acetylated GR in the morning are associated with low target-tissue sensitivity to glucocorticoids and vice versa in the evening and early night. Modified from Reference [56].