receptor downregulation
Receptor downregulation is the cell turning down the volume by removing some of its speakers. When a hormone shouts continuously, the cell protects itself from overstimulation by taking receptors off its surface, so the same hormone level now produces a weaker effect.
Mechanistically, prolonged or high hormone exposure prompts the cell to internalize receptors (pull them inside) and to make fewer new ones. With fewer receptors available to bind, the cell's sensitivity falls even though the hormone is still present at the same concentration. The opposite process, making more receptors when a hormone is scarce, is called upregulation.
Downregulation is a normal way the body adapts to sustained signals, but it has clinical consequences. In type 2 diabetes, chronically high insulin contributes to fewer or less effective receptors and reduced response — a part of insulin resistance — and continuous rather than pulsed dosing of some hormone drugs can blunt their own effect over time.
Long-term high insulin levels in obesity can lead target tissues to reduce insulin receptor signaling, contributing to the blunted response seen in insulin resistance.
Fewer receptors as an adaptation to a persistently high hormone signal.
This is one reason continuous GnRH (instead of natural pulses) eventually shuts down LH and FSH — a paradoxical effect used deliberately in some hormone therapies.