Downregulaatioon

Downregulaatioon, a variant spelling of downregulation, refers to a cellular process by which the responsiveness to a signal is reduced. The term is typically written as downregulation, and the variant spelling may appear in some texts or non-English sources. Downregulation can involve lower receptor density on the cell surface, diminished signaling efficiency, or reduced expression of a gene encoding a signaling component.

Mechanisms include receptor downregulation via endocytosis and lysosomal degradation after prolonged ligand exposure, receptor internalization with or without recycling, and decreases in receptor synthesis through reduced gene transcription. Post-translational modifications such as ubiquitination tag receptors for degradation, while recycling pathways can restore surface receptor levels in some systems.

Types include homologous downregulation, where the response to a specific ligand reduces the number or sensitivity of its own receptor, and heterologous downregulation, where signaling of other receptors is affected. Ligand-induced downregulation often contrasts with constitutive downregulation, which occurs independently of ligand binding.

Contexts include pharmacology and physiology; in pharmacology, repeated exposure to drugs can cause tolerance via receptor downregulation, diminishing drug effectiveness. In physiology, hormones and growth factors can induce downregulation of receptors to prevent overstimulation. Gene-expression downregulation involves transcriptional repression, RNA interference, or epigenetic modifications that reduce mRNA levels.