Glucocorticoid receptor

The glucocorticoid receptor (GR) or nuclear receptor subfamily 3, group C, member 1 is a ligand-activated intracytoplasmatic transcription factor  that interacts with high affinity to cortisol and other glucocorticoids.

The GR is controlled by gene NR3Cl on chromosome 5 (5q31).

Structure
Like the other steroid receptors the structure of the GR consists of a variable domain, the DNA-binding domain with zinc fingers, a hinge region, and the hormone-binding domain with a final carboxy terminal.

Binding and response
Cortisol diffuses through the cell wall into the cytoplasm and binds to the glucocorticoid receptor (GR) forming a GR-hormone complex. Initially the GR includes the heat shock protein 90 (hsp90), the heat shock protein 70 (hsp70) and the protein FKBP52 (FK506-binding protein 52). Dissociation of the GR complex releases the heat shock chaperones and yields the free cortisol-receptor subunits that link up as  homodimers. These are translocated via nucleopores into the nucleus and bind with zinc fingers to the specific DNA responsive elements activating gene transcription. The biologic response depends on the cell type.

Agonists and antagonists
Relaxin is an agonist, and RU486 and cyproterone are antagonists of the GR. Also, progesterone and DHEA have antagonist effects on the GR.

The GR is abnormal in familial glucocorticoid resistance (PMID 11932321).