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14-September-2008 11:27:26 - Downregulation and upregulation Redirected from Downregulation Downregulation is the process by which a cell decreases the number of a cellular component, such as RNA or protein, in response to an external variable. An increase of component is called upregulation. An example of downregulation is that the cell decreases the number of receptors to a given hormone or neurotransmitter to reduce its sensitivity to this molecule. This is a locally acting negative feedback mechanism. An example of upregulation is that liver cell increases the number of Cytochrome P450 enzymes when xenobiotic molecules, such as dioxin, are detected in order to degrade them. Contents 1 Receptor downregulation 1.1 Mechanism 1.2 Cases 1.3 Reversal 2 See also 3 References 4 External links Receptor downregulation Mechanism For insulin, the process of downregulation occurs when there are elevated levels of the hormone in the blood. When insulin binds to its receptors on the surface of a cell, endocytosis of the hormone receptor complex is initiated, only to be subsequently attacked by intracellular lysosomal enzymes. The internalization is multi-purposed, as it provides the pathway for degradation of the hormone and also a way to regulate the number of sites that are available for binding on the cell's surface. At high plasma concentrations, the number of surface receptors for insulin is gradually reduced by the accelerated rate of receptor internalization and degradation brought about by increased hormonal binding. The rate of synthesis of new receptors within the endoplasmic reticulum and their insertion in the plasma membrane do not keep pace with their rate of destruction. Over time, this self-induced loss of target cell receptors for insulin reduces the target cell's sensitivity to the elevated hormone concentration. The process of decreasing the number of receptor sites is virtually the same for all hormones; it only varies in the receptor hormone complex. Cases To illustrate this process we shall look at the insulin receptor sites on the target cells of a type 2 diabetic. Due to the elevated levels of blood glucose from excessive feeding in an overweight individual, the β-cells islets of Langerhans in the pancreas must release more insulin than normally emitted to match the demand and return the blood to homeostatic levels. The near-constant increase in blood insulin levels results from an effort to match the increase in blood glucose, which will cause receptor sites on the person's cell to downregulate and decrease the number of receptors for insulin, increasing the subject's resistance by decreasing sensitivity to this hormone. There is also a hepatic decrease in sensitivity to insulin. This can be seen in the continuing gluconeogenesis in the liver even when blood glucose levels are elevated. This is the more common process of insulin resistance, which in turn leads to adult onset diabetes in that subject. Other cases include Diabetes insipidus; here the kidneys become insensitive to arginine vasopressin. Reversal There are ways to counteract this process; using the previous example a type 2 diabetic may increase their sensitivity to insulin through proper diet and regular exercise producing weight loss; some may even return to their pre-diabetic state following this regimen. See also Regulation of gene expression Desensitization medicine References Sherwood, L. 2004. Human Physiology From Cells to Systems, 5th Ed p. 680. Belmont, CA: Brooks/Cole-Thomson Learning Wilmore, J., Costill, D. 2004. Physiology of Sport and Exercise, 3rd Ed p. 164. Champaign, IL: Human Kinetics External links MeSH Down-Regulation This biochemistry article is a stub. v d e Molecular Biology Central Dogma DNA Replication DNA, Transcription RNA - Translation protein gene regulation Epigenetic · genetic · post-transcriptional · post-translational regulation other key concepts mitosis · cell signalling · Post-transcriptional modification and Post-translational modification · Dry Lab/Wet lab · Development · History of molecular biology · genetic elements Promoter Pribnow box, TATA box · Operon gal operon, lac operon, trp operon · Terminator · Enhancer · Repressor lac repressor, trp repressor · Silencer · Histone methylation Techniques Cell culture · model organisms such as C57BL/6 mice · Nucleic acid methods · Protein methods High-throughput -omicsTechniques DNA microarray · Mass spectrometry · Lab-on-a-chip Linked Life science disciplines Cell Biology · Biochemistry · Computational Biology Glossary gene expression terms · Academic rank Retrieved from http://en..org/wiki/Downregulation_and_upregulation Categories: Biochemistry stubs Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Italiano This page was last modified on 8 June 2008, at 04:19
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