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Down-regulation


In the biological context of organisms' production of gene products, downregulation is the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external stimulus. The complementary process that involves increases of such components is called upregulation.

An example of downregulation is the cellular decrease in the number of receptors to a molecule, such as a hormone or neurotransmitter, which reduces the cell's sensitivity to the molecule. This is an example of a locally acting negative feedback mechanism.

An example of upregulation is the response of liver cells exposed to such xenobiotic molecules as dioxin. In this situation, the cells increase their production of , which in turn increases their degradation of these molecules.

All living cells have the ability to receive and process signals that originate outside of their walls, which they do by means of proteins called receptors, usually found on a cell's surface. When such signals bind to a receptor, they effectively direct the cell to do something, such as dividing, dying, or allowing substances to be created, or to enter or exit the cell. A cell's ability to respond to a chemical message depends on the presence of receptors tuned to that message. The more receptors a cell has that are tuned to the message, the more the cell will respond to it.

Receptors are created, or expressed, by the DNA of the cell, and they can be increased, or upregulated, when the signal is weak, or decreased, or downregulated, when it is strong.

Downregulation of receptors happens when receptors have been chronically exposed to an excessive amount of neurotransmitters, whether endogenous or drugs. This results in ligand-induced desensitization or internalization of that receptor. It is usually exhibited by various hormone receptors. Upregulation of receptors, on the other hand, results in super-sensitized receptors especially after repeated exposure to the drug.


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