Glucocorticoids (GCs) and their analogs regulate downstream gene expression through the glucocorticoid receptor (GR, also known as NR3C1), which is a member of the nuclear receptor superfamily of ligand-activated transcription factors. GCs diffuse into the cytoplasm, bind to GR, and are then translocated to the nucleus, where they bind to glucocorticoid response elements (GREs) in the promoters of target genes, thereby activating or repressing gene expression. GCs also modulate gene expression via non-GR pathways, such as through cAMP response element-binding (CREB) protein, activator protein (AP)-1, and NF-κB.
ESR1 encodes an estrogen receptor and ligand-activated transcription factor. The canonical protein contains an N-terminal ligand-independent transactivation domain, a central DNA binding domain, a hinge domain, and a C-terminal ligand-dependent transactivation domain. The protein localizes to the nucleus where it may form either a homodimer or a heterodimer with estrogen receptor 2. The protein encoded by ESR1 regulates the transcription of many estrogen-inducible genes that play a role in growth, metabolism, sexual development, gestation, and other reproductive functions and is expressed in many non-reproductive tissues. The receptor encoded by ESR1 plays a key role in breast cancer, endometrial cancer, and osteoporosis.