Glucocorticoid receptors

Transduction mechanisms
Agonists
Antagonists
Inverse agonists
Positive allosteric modulators
Negative allosteric modulators

The glucocorticoid receptor (GR) is a type of steroid receptor that binds glucocorticoids, a class of steroid hormones that play a crucial role in regulating various physiological processes, including metabolism, immune response, and stress response. The receptor is encoded by the NR3C1 gene in humans.

Structure

The glucocorticoid receptor is a ligand-dependent transcription factor that belongs to the nuclear receptor superfamily. It consists of several domains:

• N-terminal domain (NTD): This region is responsible for the transcriptional activation of the receptor and contains the activation function 1 (AF1) region.
• DNA-binding domain (DBD): This domain allows the receptor to bind to specific DNA sequences known as glucocorticoid response elements (GREs).
• Hinge region: This flexible region connects the DBD to the ligand-binding domain.
• Ligand-binding domain (LBD): This domain binds glucocorticoids, allowing the receptor to change conformation and interact with other proteins.

Function

Upon binding to glucocorticoids, the glucocorticoid receptor undergoes a conformational change that allows it to translocate from the cytoplasm to the nucleus. In the nucleus, the receptor binds to GREs in the DNA, either upregulating or downregulating the expression of target genes. The GR can also interact with other transcription factors such as NF-κB and AP-1, modulating their activity.

Clinical significance

Glucocorticoid receptors are critical in the therapeutic effects of glucocorticoids used to treat a variety of conditions, including asthma, allergies, and autoimmune diseases. Abnormalities in glucocorticoid receptor function can lead to diseases such as glucocorticoid resistance syndrome, where the body's response to glucocorticoids is diminished.

Pharmacology

The pharmacological manipulation of glucocorticoid receptors is a research area focused on developing drugs that can selectively modulate receptor activity. This includes the development of selective glucocorticoid receptor agonists (SEGRAs) and modulators (SGRMs) that aim to provide the anti-inflammatory benefits of glucocorticoids while minimizing side effects.

See also

• Steroid hormone receptor
• Mineralocorticoid receptor
• Nuclear receptor