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45-413: The abbreviation DSIP can have different meanings: Delta sleep-inducing peptide Revolutionary Socialist Workers' Party (Turkey) Devrimci Sosyalist İşçi Partisi, (DSİP) Disability Service Improvement Program ( Social Security Administration ) Topics referred to by the same term [REDACTED] This disambiguation page lists articles associated with

90-477: A class of corticosteroids , which are a class of steroid hormones . Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebrate animal cell. The name "glucocorticoid" is a portmanteau ( gluco se + cort ex + ster oid ) and is composed from its role in regulation of glucose metabolism , synthesis in the adrenal cortex , and its steroidal structure (see structure below). Glucocorticoids are part of

135-427: A dose that provides approximately the same glucocorticoid effects as normal cortisol production; this is referred to as physiologic, replacement, or maintenance dosing. This is approximately 6–12 mg/m /day of hydrocortisone (m refers to body surface area (BSA), and is a measure of body size; an average man's BSA is 1.9 m ). Glucocorticoids cause immunosuppression , and the therapeutic component of this effect

180-445: A few days begins to produce suppression of the patient's adrenal glands suppressing hypothalamic corticotropin-releasing hormone (CRH) leading to suppressed production of adrenocorticotropic hormone (ACTH) by the anterior pituitary. With prolonged suppression, the adrenal glands atrophy (physically shrink), and can take months to recover full function after discontinuation of the exogenous glucocorticoid. During this recovery time,

225-436: A lesser extent, after treatment, a condition known as " steroid dementia ". Glucocorticoids could act centrally, as well as peripherally, to assist in the normalization of extracellular fluid volume by regulating body's action to atrial natriuretic peptide (ANP). Centrally, glucocorticoids could inhibit dehydration-induced water intake; peripherally, glucocorticoids could induce a potent diuresis. Glucocorticoids bind to

270-600: A multitude of less-dramatic physiologic roles for glucocorticoids. Glucocorticoids have multiple effects on fetal development. An important example is their role in promoting maturation of the lung and production of the surfactant necessary for extrauterine lung function. Mice with homozygous disruptions in the corticotropin -releasing hormone gene (see below) die at birth due to pulmonary immaturity. In addition, glucocorticoids are necessary for normal brain development, by initiating terminal maturation, remodeling axons and dendrites, and affecting cell survival and may also play

315-488: A role in hippocampal development . Glucocorticoids stimulate the maturation of the Na /K /ATPase, nutrient transporters, and digestion enzymes, promoting the development of a functioning gastro-intestinal system. Glucocorticoids also support the development of the neonate's renal system by increasing glomerular filtration. Glucocorticoids act on the hippocampus , amygdala , and frontal lobes . Along with adrenaline , these enhance

360-878: A significant impact on vigilance ( attention deficit disorder ) and cognition (memory). This appears to follow the Yerkes-Dodson curve , as studies have shown circulating levels of glucocorticoids vs. memory performance follow an upside-down U pattern, much like the Yerkes-Dodson curve. For example, long-term potentiation (LTP; the process of forming long-term memories) is optimal when glucocorticoid levels are mildly elevated, whereas significant decreases of LTP are observed after adrenalectomy (low-glucocorticoid state) or after exogenous glucocorticoid administration (high-glucocorticoid state). Elevated levels of glucocorticoids enhance memory for emotionally arousing events, but lead more often than not to poor memory for material unrelated to

405-424: A wide range of effects, including, for example: The opposite mechanism is called transcriptional repression, or transrepression . The classical understanding of this mechanism is that activated glucocorticoid receptor binds to DNA in the same site where another transcription factor would bind, which prevents the transcription of genes that are transcribed via the activity of that factor. While this does occur,

450-517: Is Trp - Ala - Gly -Gly- Asp -Ala- Ser -Gly- Glu (WAGGDASGE). The gene has yet to be found in rabbits, along with any receptors or precursor peptides. However, searches through BLAST have found that it aligns with a hypothetical Amycolatopsis coloradensis protein. This could indicate that DSIP has a bacterial origin. Delta-sleep-inducing peptide was first discovered in 1974 by the Swiss Schoenenberger-Monnier group who isolated it from

495-434: Is abundant in the gut secretory cells and in the pancreas where it co-localises with glucagon . In the brain its action may be mediated by NMDA receptors . In another study delta-sleep-inducing peptide stimulated acetyltransferase activity through α 1 receptors in rats. It is unknown where DSIP is synthesized. In vitro it has been found to have a low molecular stability with a half life of only 15 minutes due to

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540-403: Is complicated. Dexamethasone decreases IFN-gamma stimulated Fc gamma RI expression in neutrophils while conversely causing an increase in monocytes . Glucocorticoids may also decrease the expression of Fc receptors in macrophages, but the evidence supporting this regulation in earlier studies has been questioned. The effect of Fc receptor expression in macrophages is important since it

585-412: Is mainly the decreases in the function and numbers of lymphocytes , including both B cells and T cells . The major mechanism for this immunosuppression is through inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells ( NF-κB ). NF-κB is a critical transcription factor involved in the synthesis of many mediators (i.e., cytokines) and proteins (i.e., adhesion proteins) that promote

630-669: Is more prominent in immature T cells still inside in the thymus, but peripheral T cells are also affected. The exact mechanism regulating this glucocorticoid sensitivity lies in the Bcl-2 gene. Glucocorticoids also suppress the humoral immunity , thereby causing a humoral immune deficiency . Glucocorticoids cause B cells to express smaller amounts of IL-2 and of IL-2 receptors . This diminishes both B cell clone expansion and antibody synthesis. The diminished amounts of IL-2 also cause fewer T lymphocyte cells to be activated. The effect of glucocorticoids on Fc receptor expression in immune cells

675-662: Is necessary for the phagocytosis of opsonised cells. This is because Fc receptors bind antibodies attached to cells targeted for destruction by macrophages. Glucocorticoids are potent anti-inflammatories, regardless of the inflammation's cause; their primary anti-inflammatory mechanism is lipocortin-1 (annexin-1) synthesis. Lipocortin-1 both suppresses phospholipase A2 , thereby blocking eicosanoid production, and inhibits various leukocyte inflammatory events ( epithelial adhesion , emigration , chemotaxis , phagocytosis , respiratory burst , etc.). In other words, glucocorticoids not only suppress immune response, but also inhibit

720-669: Is released when a glucocorticoid binds to glucocorticoid receptor, and phosphorylates a protein that in turn displaces an adaptor protein from a receptor important in inflammation, epidermal growth factor , reducing its activity, which in turn results in reduced creation of arachidonic acid – a key proinflammatory molecule. This is one mechanism by which glucocorticoids have an anti-inflammatory effect. A variety of synthetic glucocorticoids, some far more potent than cortisol, have been created for therapeutic use. They differ in both pharmacokinetics (absorption factor, half-life, volume of distribution, clearance) and pharmacodynamics (for example

765-740: Is the name used for pharmaceutical preparations of cortisol. The data below refer to oral administration. Oral potency may be less than parenteral potency because significant amounts (up to 50% in some cases) may not reach the circulation. Fludrocortisone acetate and deoxycorticosterone acetate are, by definition, mineralocorticoids rather than glucocorticoids, but they do have minor glucocorticoid potency and are included in this table to provide perspective on mineralocorticoid potency. Glucocorticoids may be used in low doses in adrenal insufficiency . In much higher doses, oral or inhaled glucocorticoids are used to suppress various allergic , inflammatory , and autoimmune disorders. Inhaled glucocorticoids are

810-719: The MAPK cascade and is homologous to glucocorticoid-induced leucine zipper (GILZ). GILZ can be induced by Dexamethasone . It prevents Raf-1 activation, which inhibits phosphorylation and activation of ERK . Many roles for DSIP have been suggested following research carried out using peptide analogues with a greater molecular stability and through measuring DSIP-like immunological (DSIP-LI) response by injecting DSIP antiserum and antibodies . Safety and possible side-effects of long-term DSIP use haven't been established in clinical research studies. Glucocorticoids Glucocorticoids (or, less commonly, glucocorticosteroids ) are

855-558: The adrenal cortex ), but is often used as a synonym for "glucocorticoid". Glucocorticoids are chiefly produced in the zona fasciculata of the adrenal cortex , whereas mineralocorticoids are synthesized in the zona glomerulosa . Cortisol (or hydrocortisone) is the most important human glucocorticoid. It is essential for life , and it regulates or supports a variety of important cardiovascular , metabolic , immunologic , and homeostatic functions. Increases in glucocorticoid concentrations are an integral part of stress response and are

900-435: The feedback mechanism in the immune system , which reduces certain aspects of immune function, such as inflammation . They are therefore used in medicine to treat diseases caused by an overactive immune system , such as allergies , asthma , autoimmune diseases , and sepsis . Glucocorticoids have many diverse effects such as pleiotropy , including potentially harmful side effects . They also interfere with some of

945-412: The hypothalamus , limbic system and pituitary as well as various peripheral organs, tissues and body fluids. In the pituitary it co-localises with many peptide and non-peptide mediators such as corticotropin-like intermediate peptide (CLIP), adrenocorticotrophic hormone (ACTH), melanocyte-stimulating hormone (MSH), thyroid-stimulating hormone (TSH) and melanin concentrating hormone (MCH). It

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990-416: The abnormal mechanisms in cancer cells , so they are used in high doses to treat cancer. This includes inhibitory effects on lymphocyte proliferation, as in the treatment of lymphomas and leukemias , and the mitigation of side effects of anticancer drugs . Glucocorticoids affect cells by binding to the glucocorticoid receptor . The activated glucocorticoid receptor-glucocorticoid complex up-regulates

1035-427: The action of a specific aminopeptidase -like enzyme. It has been suggested that in the body it complexes with carrier proteins to prevent degradation, or exists as a component of a large precursor molecule, but as yet no structure or gene has been found for this precursor. Evidence supports the current belief that it is regulated by glucocorticoids . Gimble et al. suggest that DSIP interacts with components of

1080-502: The advantage of only affecting the targeted area, thereby reducing side effects or potential interactions. In this case, the main compounds used are beclometasone , budesonide , fluticasone , mometasone and ciclesonide . In rhinitis, sprays are used. For asthma, glucocorticoids are administered as inhalants with a metered-dose or dry powder inhaler . In rare cases, symptoms of radiation induced thyroiditis has been treated with oral glucocorticoids. Glucocorticoids can be used in

1125-670: The body's immune system. Glucocorticoid effects may be broadly classified into two major categories: immunological and metabolic . In addition, glucocorticoids play important roles in fetal development and body fluid homeostasis. Glucocorticoids function via interaction with the glucocorticoid receptor: Glucocorticoids are also shown to play a role in the development and homeostasis of T lymphocytes . This has been shown in transgenic mice with either increased or decreased sensitivity of T cell lineage to glucocorticoids. The name "glucocorticoid" derives from early observations that these hormones were involved in glucose metabolism . In

1170-447: The capacity of mineralocorticoid activity: retention of sodium (Na ) and water ; renal physiology ). Because they permeate the intestines easily, they are administered primarily per os ( by mouth ), but also by other methods, such as topically on skin . More than 90% of them bind different plasma proteins , though with a different binding specificity. Endogenous glucocorticoids and some synthetic corticoids have high affinity to

1215-496: The cerebral venous blood of rabbits in an induced state of sleep. It was primarily believed to be involved in sleep regulation due to its apparent ability to induce slow-wave sleep in rabbits, but studies on the subject have been contradictory. DSIP-like material has been found in human breast milk. DSIP is an amphiphilic peptide of molecular weight 850 daltons with the amino acid motif: N-Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu-C It has been found in both free and bound forms in

1260-531: The cytosolic glucocorticoid receptor , a type of nuclear receptor that is activated by ligand binding. After a hormone binds to the corresponding receptor, the newly formed complex translocates itself into the cell nucleus , where it binds to glucocorticoid response elements in the promoter region of the target genes resulting in the regulation of gene expression . This process is commonly referred to as transcriptional activation, or transactivation . The proteins encoded by these up-regulated genes have

1305-646: The elaboration of selectively acting glucocorticoid drugs. Side effects include: In high doses, hydrocortisone (cortisol) and those glucocorticoids with appreciable mineralocorticoid potency can exert a mineralocorticoid effect as well, although in physiologic doses this is prevented by rapid degradation of cortisol by 11β-hydroxysteroid dehydrogenase isoenzyme 2 ( 11β-HSD2 ) in mineralocorticoid target tissues. Mineralocorticoid effects can include salt and water retention, extracellular fluid volume expansion, hypertension , potassium depletion, and metabolic alkalosis . Glucocorticoids cause immunosuppression , decreasing

1350-584: The expression of anti-inflammatory proteins in the nucleus (a process known as transactivation ) and represses the expression of pro-inflammatory proteins in the cytosol by preventing the translocation of other transcription factors from the cytosol into the nucleus ( transrepression ). Glucocorticoids are distinguished from mineralocorticoids and sex steroids by their specific receptors , target cells , and effects. In technical terms, " corticosteroid " refers to both glucocorticoids and mineralocorticoids (as both are mimics of hormones produced by

1395-535: The fasted state, cortisol stimulates several processes that collectively serve to increase and maintain normal concentrations of glucose in the blood. Metabolic effects: Excessive glucocorticoid levels resulting from administration as a drug or hyperadrenocorticism have effects on many systems. Some examples include inhibition of bone formation, suppression of calcium absorption (both of which can lead to osteoporosis ), delayed wound healing, muscle weakness, and increased risk of infection. These observations suggest

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1440-423: The formation of flashbulb memories of events associated with strong emotions, both positive and negative. This has been confirmed in studies, whereby blockade of either glucocorticoids or noradrenaline activity impaired the recall of emotionally relevant information. Additional sources have shown subjects whose fear learning was accompanied by high cortisol levels had better consolidation of this memory (this effect

1485-426: The function and/or numbers of neutrophils , lymphocytes (including both B cells and T cells ), monocytes , macrophages , and the anatomical barrier function of the skin. This suppression, if large enough, can cause manifestations of immunodeficiency , including T cell deficiency , humoral immune deficiency and neutropenia . In addition to the effects listed above, use of high-dose glucocorticoids for only

1530-701: The function of other transcription factors. This latter mechanism appears to be the most likely way that activated glucocorticoid receptor interferes with NF-κB - namely by recruiting histone deacetylase , which deacetylate the DNA in the promoter region leading to closing of the chromatin structure where NF-κB needs to bind. Activated glucocorticoid receptor has effects that have been experimentally shown to be independent of any effects on transcription and can only be due to direct binding of activated glucocorticoid receptor with other proteins or with mRNA. For example, Src kinase which binds to inactive glucocorticoid receptor,

1575-561: The immune response. Inhibition of this transcription factor, therefore, blunts the capacity of the immune system to mount a response. Glucocorticoids suppress cell-mediated immunity by inhibiting genes that code for the cytokines IL-1 , IL-2 , IL-3 , IL-4 , IL-5 , IL-6 , IL-8 and IFN-γ, the most important of which is IL-2. Smaller cytokine production reduces the T cell proliferation. Glucocorticoids, however, not only reduce T cell proliferation, but also lead to another well known effect - glucocorticoid-induced apoptosis. The effect

1620-538: The management of familial hyperaldosteronism type 1 . They are not effective, however, for use in the type 2 condition. Glucocorticoids could be used in the treatment of decompensated heart failure to potentiate renal responsiveness to diuretics, especially in heart failure patients with refractory diuretic resistance with large doses of loop diuretics. Resistance to the therapeutic uses of glucocorticoids can present difficulty; for instance, 25% of cases of severe asthma may be unresponsive to steroids. This may be

1665-421: The most commonly used biomarkers to measure stress. Glucocorticoids have numerous non-stress-related functions as well, and glucocorticoid concentrations can increase in response to pleasure or excitement. Various synthetic glucocorticoids are available; these are widely utilized in general medical practice and numerous specialties , either as replacement therapy in glucocorticoid deficiency or to suppress

1710-417: The protein transcortin (also called corticosteroid-binding globulin), whereas all of them bind albumin . In the liver, they quickly metabolize by conjugation with a sulfate or glucuronic acid , and are secreted in the urine . Glucocorticoid potency, duration of effect, and the overlapping mineralocorticoid potency vary. Cortisol is the standard of comparison for glucocorticoid potency. Hydrocortisone

1755-500: The result of genetic predisposition, ongoing exposure to the cause of the inflammation (such as allergens ), immunological phenomena that bypass glucocorticoids, pharmacokinetic disturbances (incomplete absorption or accelerated excretion or metabolism) and viral and/or bacterial respiratory infections. Glucocorticoid drugs currently being used act nonselectively, so in the long run they may impair many healthy anabolic processes. To prevent this, much research has been focused recently on

1800-404: The results are not consistent for all cell types and conditions; there is no generally accepted, general mechanism for transrepression. New mechanisms are being discovered where transcription is repressed, but the activated glucocorticoid receptor is not interacting with DNA, but rather with another transcription factor directly, thus interfering with it, or with other proteins that interfere with

1845-711: The second-line treatment for asthma . They are also administered as post-transplantory immunosuppressants to prevent the acute transplant rejection and the graft-versus-host disease . Nevertheless, they do not prevent an infection and also inhibit later reparative processes . Newly emerging evidence showed that glucocorticoids could be used in the treatment of heart failure to increase the renal responsiveness to diuretics and natriuretic peptides. Glucocorticoids are historically used for pain relief in inflammatory conditions. However, corticosteroids show limited efficacy in pain relief and potential adverse events for their use in tendinopathies . Any glucocorticoid can be given in

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1890-408: The source of stress/emotional arousal. In contrast to the dose-dependent enhancing effects of glucocorticoids on memory consolidation, these stress hormones have been shown to inhibit the retrieval of already stored information. Long-term exposure to glucocorticoid medications, such as asthma and anti-inflammatory medication, has been shown to create deficits in memory and attention both during and, to

1935-479: The title DSIP . If an internal link led you here, you may wish to change the link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=DSIP&oldid=1019947349 " Category : Disambiguation pages Hidden categories: Short description is different from Wikidata All article disambiguation pages All disambiguation pages Delta sleep-inducing peptide Its amino acid sequence

1980-570: The two main products of inflammation, prostaglandins and leukotrienes . They inhibit prostaglandin synthesis at the level of phospholipase A2 as well as at the level of cyclooxygenase /PGE isomerase (COX-1 and COX-2), the latter effect being much like that of NSAIDs , thus potentiating the anti-inflammatory effect. In addition, glucocorticoids also suppress cyclooxygenase expression. Glucocorticoids marketed as anti-inflammatories are often topical formulations, such as nasal sprays for rhinitis or inhalers for asthma . These preparations have

2025-483: Was more important in men). The effect that glucocorticoids have on memory may be due to damage specifically to the CA1 area of the hippocampal formation. In multiple animal studies, prolonged stress (causing prolonged increases in glucocorticoid levels) have shown destruction of the neurons in the hippocampus area of the brain, which has been connected to lower memory performance. Glucocorticoids have also been shown to have

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