NR3C - nuclear receptor subfamily 3 group C member | Elisa - Clia - Antibody - Protein

Background

NR3C refers to a group of receptors within the nuclear receptor subfamily 3, group C, which includes some of the most well-studied receptors, such as the glucocorticoid receptor (NR3C1), mineralocorticoid receptor (NR3C2), progesterone receptor (NR3C3), and androgen receptor (NR3C4). These receptors are essential for mediating the effects of steroid hormones on gene expression. They are involved in a wide range of physiological processes including stress response, immune function, metabolism, electrolyte balance, and reproductive health. Dysregulation of NR3C receptors is implicated in various diseases, including cancer, metabolic disorders, and cardiovascular diseases.

Protein Structure

The structure of NR3C family members is highly conserved and typically includes the following domains:

• N-terminal Domain (NTD): This domain is involved in transcriptional activation and contains activation function-1 (AF-1). It is highly variable in length and sequence among family members.
• DNA-binding Domain (DBD): Comprising two zinc finger motifs, this domain binds to specific hormone response elements (HREs) in the DNA to regulate gene transcription.
• Hinge Region: Provides flexibility to the receptor and contains nuclear localization signals necessary for the transport of the receptor to the nucleus.
• Ligand-binding Domain (LBD): This domain binds to the steroid hormone and contains activation function-2 (AF-2). It is crucial for receptor dimerization, interaction with co-regulators, and the initiation of transcriptional activity.

Classification and Subtypes

NR3C receptors are classified based on the type of steroid hormone they bind to:

• Glucocorticoid Receptor (NR3C1): Binds glucocorticoids like cortisol.
• Mineralocorticoid Receptor (NR3C2): Binds mineralocorticoids such as aldosterone.
• Progesterone Receptor (NR3C3): Binds progesterone.
• Androgen Receptor (NR3C4): Binds androgens like testosterone and dihydrotestosterone.

Each of these receptors can exist in different isoforms due to alternative splicing, adding another layer of functional diversity.

Function and Biological Significance

NR3C receptors play pivotal roles in:

• Regulating Gene Expression: They modulate the transcription of target genes by binding to specific response elements in the DNA.
• Metabolism: Glucocorticoid receptors regulate glucose metabolism and immune responses.
• Electrolyte Balance: Mineralocorticoid receptors control sodium and water balance in the kidneys.
• Reproductive Health: Progesterone and androgen receptors are essential for reproductive system development and function.
• Stress Response: Glucocorticoid receptors are crucial for mediating the body's response to stress.

Clinical Issues

• Cancer: Dysregulation of NR3C receptors, particularly the androgen receptor, is a hallmark of prostate cancer.
• Metabolic Disorders: Abnormal glucocorticoid receptor function can lead to conditions like Cushing's syndrome and metabolic syndrome.
• Cardiovascular Diseases: Mineralocorticoid receptor overactivity is linked to hypertension and heart failure.
• Reproductive Disorders: Mutations in the progesterone or androgen receptors can result in infertility and other reproductive issues.

Summary

The NR3C family comprises critical nuclear receptors that mediate the effects of steroid hormones on gene expression, impacting a wide range of physiological processes. These receptors share a conserved structure with distinct functional domains, enabling them to bind specific hormones and regulate target genes. Their roles in metabolism, stress response, electrolyte balance, and reproduction underline their importance in health and disease. Understanding the structure and function of NR3C receptors is essential for developing targeted therapies for related disorders.