When glucocorticoid receptor meets the mineralocorticoid receptor in human cells

Glucocorticoids are widely used to treat a variety of inflammatory diseases. Mechanistically glucocorticoid ligands induce glucocorticoid receptor (GR) homodimerization and regulation of gene expression. Here we show that GR and mineralocorticoid receptor (MR) form molecular complexes with distinct transcriptional responses that alter the biological roles of GR. MR inhibited GR interaction with genomic DNA and diminished glucocorticoid-regulated gene expression as well as suppressed cell apoptosis induced by GR signaling. Cell lines expressing GR, MR, or GR + MR were developed using human U-2OS cell line. These cell lines were treated with dexamethasone (1 nM or 10 nM) or aldosterone (1 nM) and transcriptomes in the cells were compared by RNAseq analyses. GR and MR functional interaction for the gene regulation was observed.