Receptor Downregulation

A decrease in the number of functional receptors on the cell surface, typically in response to prolonged or excessive agonist stimulation. Mechanisms include receptor internalization via endocytosis, lysosomal degradation, and reduced gene transcription. Clinically, downregulation contributes to drug tolerance and is exploited therapeutically by GnRH agonists.

Examples

• Beta-adrenergic receptor downregulation with chronic isoproterenol
• GnRH receptor downregulation by leuprolide (prostate cancer)
• Insulin receptor downregulation in hyperinsulinemia