Gene expression profiling of dexamethasone effects in multiple tissues

Glucocorticoids, acting through the glucocorticoid receptor (GR), control metabolism, maintain homeostasis, and enable adaptive responses to environmental challenges. Their function has been comprehensively studied, leading to the identification of numerous tissue-specific GR-dependent mechanisms. We examine the cross-tissue effects of GR activation on gene expression. We assessed changes induced by stimulation with GR agonist, dexamethasone in nine tissues (adrenal cortex, perigonadal adipose tissue, hypothalamus, liver, kidney, anterior thigh muscle, pituitary gland, spleen, and lungs) in adult male C57BL/6 mice, using whole-genome microarrays. Likewise, we leveraged existing gene annotations and created new annotation sets based on chromatin immunoprecipitation sequencing, recent large-scale genome-wide association studies, and human transcriptome collections. We found novel links between regulated gene patterns and human phenotypic traits. Overall effects of GR stimulation are well coordinated and closely linked to the biological roles of tissues and organs. Our findings provide novel insights into complex systemic and tissue-specific actions of glucocorticoids and their potential impacts on human physiology and pathology.