The process by which a receptor becomes less responsive to its ligand after sustained or repeated stimulation. This is the body’s built-in volume control—when a signal persists, the cell dials down the receptor’s sensitivity to prevent overstimulation.

Desensitization occurs through several mechanisms: the receptor may be internalized (pulled inside the cell), phosphorylated (chemically modified to reduce signaling), or downregulated (fewer receptors produced). This phenomenon is clinically significant for peptide therapeutics—it explains why some GH secretagogues lose effectiveness over time, why GnRH agonists like leuprolide initially stimulate and then suppress hormone production, and why continuous versus pulsatile dosing can produce opposite effects.