Down regulation is the process by which a 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 increase of receptors is called up regulation. Drawing of the structure of cork as it appeared under the microscope to Robert Hooke from Micrographia which is the origin of the word cell. Cells in culture, stained for keratin (red) and DNA (green). ... In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ... Norepinephrine A hormone (from Greek όρμή - to set in motion) is a chemical messenger from one cell (or group of cells) to another. ... Chemical structure of D-Aspartic Acid, a common Amino Acid neurotransmitter. ... Negative feedback (shortened to NFB) is a type of feedback in which the system responds in an opposite direction to the perturbation. ... Upregulation is the process by which a cell increases the number of receptors to a given hormone or neurotransmitter to improve its sensitivity to this molecule. ...

Mechanism

For insulin, the process of down regulation 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. Endocytosis is a process whereby cells absorb material (molecules such as proteins) from the outside by engulfing it with their cell membrane. ... Lysosomes are organelles in animal cells that contain digestive enzymes (acid hydrolases) to digest macromolecules. ... Neuraminidase ribbon diagram An enzyme (in Greek en = in and zyme = blend) is a protein, or protein complex, that catalyzes a chemical reaction and also controls the 3D orientation of the catalyzed substrates. ... Synthesis (from the ancient Greek σύν (with) and θεσις (placing), is commonly understood to be an integration of two or more pre-existing elements which results in a new creation. ... The endoplasmic reticulum (endoplasmic meaning within the cytoplasm, reticulum meaning little net in Latin) or ER is an organelle found in all eukaryotic cells that is an interconnected network of tubules, vesicles and cisternae that is responsible for several specialized functions: Protein translation, folding, and transport of proteins (e. ...

Cases

To illustrate this process we shall look at the insulin receptor sites on the target cells of a Type II 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 down-regulate 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 a case of adult onset diabetes in that subject. Other cases include Diabetes insipidus; here the kidneys become insensitive to arginine vasopressin. Target cells are the sites where hormones act. ... This article is about the disease that features high blood sugar. ... Glucose (Glc), a monosaccharide (or simple sugar), is the most important carbohydrate in biology. ... Beta cells are a type of cell in the pancreas in areas called the islets of Langerhans. ... The endocrine (i. ... The pancreas is an organ in the digestive and endocrine system that serves two major functions: exocrine (producing pancreatic juice containing digestive enzymes) and endocrine (producing several important hormones, including insulin). ... Homeostasis or homoeostasis is the property of an open system, especially living organisms, to regulate its internal environment so as to maintain a stable condition, by means of multiple dynamic equilibrium adjustments controlled by interrelated regulation mechanisms. ... Insulin (from Latin insula, island, as it is produced in the Islets of Langerhans in the pancreas) is a polypeptide hormone that regulates carbohydrate metabolism. ... Pyruvic acid Oxaloacetic acid Phosphoenolpyruvate Fructose 1,6-bisphosphate Fructose 6-phosphate Glucose-6-phosphate Glucose Gluconeogenesis is the generation of glucose from non-sugar carbon substrates like pyruvate, lactate, glycerol, and amino acids (primarily alanine and glutamine). ... Insulin resistance is the condition in which normal amounts of insulin are inadequate to produce a normal insulin response from fat, muscle and liver cells. ... Diabetes insipidus (DI) is a disease characterized by excretion of large amounts of severely diluted urine, which cannot be reduced when fluid intake is reduced. ... Antidiuretic hormone (ADH), or arginine vasopressin (AVP), is a peptide hormone produced by the hypothalamus, and stored in the posterior part of the pituitary gland. ...

Reversal

There are ways to counteract this process; using the previous example a Type II 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)

Gene modulation redirects here. ... For medical purposes, desensitization is a method to reduce or eliminate an organisms negative reaction to a substance or stimulus. ...

Reference

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