Down regulation
When downregulation (English: downregulation ) is referred to by a sustained high ligand - concentration induced reduction in the number of receptors on a cell , including the removal of the receptors. If there is a lack of receptors, the ligand can no longer develop its effect on the target organ , regardless of its concentration in the blood . This temporal limitation of the ligand effect serves to protect the cell or the organism .
Mechanism in peptide hormones
If peptide - hormones are bound for a longer period to the hormone receptor of the target cell, there is a lateral displacement of the hormone-receptor complexes on the cell membrane . If there is a long-term excess of hormones, clusters of these hormone-receptor complexes form in special areas (so-called “coated pits” ) of the cell membrane. These are absorbed ( internalized ) into the cell interior via endocytosis . Long-term excess of hormones thus reduces the number of receptors on the surface of the target cells, making them less sensitive to the hormone. Most peptide hormones are therefore released in bursts ( pulsatile ), whereby the down-regulation is prevented physiologically .
Another important mechanism in the regulation of the receptor density are phosphorylation effects, which lead to an internalization of the receptors and to a loss of effectiveness due to binding to arrestins or a change in conformation .