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 expression of a specific receptor in response to its increased activation by 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 cytochrome P450 enzymes, which in turn increases degradation of these dioxin molecules. Downregulation or upregulation of an RNA or protein may also arise by an epigenetic alteration. Such an epigenetic alteration can cause expression of the RNA or protein to no longer respond to an external stimulus. This occurs, for instance, during drug addiction or progression to cancer. Downregulation and upregulation of receptors All living cells have the ability to receive and process signals that originate outside their membranes, which they do by means of proteins called receptors, often located at the cell's surface imbedded in the plasma membrane. When such signals interact with 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, from instructions in 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. Their level can also be up or down regulated by modulation of systems that degrade receptors when they are no longer required by the cell. Downregulation of receptors can also occur when receptors have been chronically exposed to an excessive amount of a ligand, either from endogenous mediators or from exogenous drugs. This results in ligand-induced desensitization or internalization of that receptor. This is typically seen in animal hormone receptors. Upregulation of receptors, on