Down-regulation

Down-regulation is a cellular process that decreases the quantity of a cellular component, such as RNA or protein, in response to an external variable. An increase in the quantity of cellular component is called up-regulation.

Overview

In the process of down-regulation, the number or sensitivity of cellular receptors for a specific substance is reduced in order to decrease the cell's sensitivity to that substance. This is a form of negative feedback regulation, and can occur with hormones, neurotransmitters, and other cellular regulators.

Down-regulation occurs when a cell is repeatedly exposed to an external stimulus. This repeated exposure causes the cell to decrease its response to the stimulus by reducing the number of receptors available for binding. This can occur at the genetic level, with the cell reducing the amount of mRNA produced for the receptor protein, or at the protein level, with the cell internalizing the receptor and degrading it.

Mechanism

The mechanism of down-regulation involves a decrease in the number of receptors to a hormone or neurotransmitter on a cell's surface. This can occur through endocytosis, where the cell absorbs the receptor into its interior and degrades it. Alternatively, the cell can decrease the amount of mRNA produced for the receptor protein, reducing the number of receptors synthesized.

Clinical significance

Down-regulation has significant implications in medicine and pharmacology. For example, prolonged use of certain drugs can lead to down-regulation of the receptors that the drug targets, leading to tolerance and requiring higher doses of the drug to achieve the same effect. This is seen in conditions such as asthma, where prolonged use of beta-agonists can lead to down-regulation of beta-receptors, reducing the effectiveness of the drugs.

See also

• Up-regulation
• Endocytosis
• Negative feedback
• Pharmacology
• Tolerance (medicine)

References

Down-regulation Resources
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