cortisol cortisol cortisol names iupac name 11β,17α,21-trihydroxypregn-4-ene-3,20-dione systematic iupac name (1r,3as,3bs,9ar,9bs,11as)-1,10-dihydroxy-1-(hydroxyacetyl)-9a,11a-dimethyl-1,2,3,3a,3b,4,5,8,9,9a,9b,10,11,11a-tetradecahydro-7h-cyclopentaphenanthen-7-one identifiers cas number 50-23-7 3d model (jsmol) interactive image chebi chebi:17650 chembl chembl389621 chemspider 5551 drugbank db00741 echa infocard 100.000.019 kegg d00088 pubchem cid 5754 unii wi4x0x7bpj comptox dashboard (epa) dtxsid7020714 inchi inchi=1s/c21h30o5/c1-19-7-5-13(23)9-12(19)3-4-14-15-6-8-21(26,17(25)11-22)20(15,2)10-16(24)18(14)19/h9,14-16,18,22,24,26h,3-8,10-11h2,1-2h3/t14-,15-,16-,18+,19-,20-,21-/m0/s1key: jygxadmdtfjgbt-vwumjdoosa-n smiles o=c4\c=c2/(1(o)c3((o)(c(=o)co)cc31cc2)c)(c)cc4 properties chemical formula c21h30o5 molar mass 362.460 g/mol except where otherwise noted, data are given for materials in their standard state (at 25 °c , 100 kpa). infobox references this article is about the natural hormone. for the medication, see hydrocortisone. not to be confused with cortisone, a metabolite of cortisol, with a similar name, genesis, and function. cortisol is a steroid hormone, in the glucocorticoid class of hormones. when used as a medication, it is known as hydrocortisone. it is produced in many animals, mainly by the zona fasciculata of the adrenal cortex in the adrenal gland. it is produced in other tissues in lower quantities. it is released with a diurnal cycle and its release is increased in response to stress and low blood-glucose concentration. it functions to increase blood sugar through gluconeogenesis, to suppress the immune system, and to aid in the metabolism of fat, protein, and carbohydrates. it also decreases bone formation. many of these functions are carried out by cortisol binding to glucocorticoid or mineralocorticoid receptors inside the cell, which then bind to dna to impact gene expression. health effects metabolism of glucose in general, cortisol stimulates gluconeogenesis (the synthesis of 'new' glucose from non-carbohydrate sources, which occurs mainly in the liver, but also in the kidneys and small intestine under certain circumstances). the net effect is an increase in the concentration of glucose in the blood, further complemented by a decrease in the sensitivity of peripheral tissue to insulin, thus preventing this tissue from taking the glucose from the blood. cortisol has a permissive effect on the actions of hormones that increase glucose production, such as glucagon and adrenaline. cortisol also plays an important, but indirect, role in liver and muscle glycogenolysis (the breaking down of glycogen to glucose-1-phosphate and glucose) which occurs as a result of the action of glucagon and adrenaline. additionally, cortisol facilitates the activation of glycogen phosphorylase, which is necessary for adrenaline to have an effect on glycogenolysis. paradoxically, cortisol promotes not only gluconeogenesis in the liver, but also glycogenesis. cortisol is thus better thought of as stimulating glucose/glycogen turnover in the liver. this is in contrast to cortisol's effect in the skeletal muscle where glycogenolysis is promoted indirectly through catecholamines. metabolism of proteins and lipids elevated levels of cortisol, if prolonged, can lead to proteolysis (breakdown of proteins) and muscle wasting. the reason for proteolysis is to provide the relevant tissue with a feedstock for gluconeogenesis; see glucogenic amino acids. the effects of cortisol on lipid metabolism are more complicated since lipogenesis is observed in patients with chronic, raised circulating glucocorticoid (i.e. cortisol) levels, although an acute increase in circulating cortisol promotes lipolysis. the usual explanation to account for this apparent discrepancy is that the raised blood glucose concentration (through the action of cortisol) will stimulate insulin release. insulin stimulates lipogenesis, so this is an indirect consequence of the raised cortisol concentration in the blood but it will only occur over a longer time scale. immune response cortisol prevents the release of substances in the body that cause inflammation. it is used to treat conditions resulting from overactivity of the b-cell-mediated antibody response. examples include inflammatory and rheumatoid diseases, as well as allergies. low-dose topical hydrocortisone, available as a nonprescription medicine in some countries, is used to treat skin problems such as rashes and eczema. cortisol inhibits production of interleukin 12 (il-12), interferon gamma (ifn-gamma), ifn-alpha, and tumor necrosis factor alpha (tnf-alpha) by antigen-presenting cells (apcs) and t helper cells (th1 cells), but upregulates interleukin 4, interleukin 10, and interleukin 13 by th2 cells. this results in a shift toward a th2 immune response rather than general immunosuppression. the activation of the stress system (and resulting increase in cortisol and th2 shift) seen during an infection is believed to be a protective mechanism which prevents an over-activation of the inflammatory response. cortisol can weaken the activity of the immune system. it prevents proliferation of t-cells by rendering the interleukin-2 producer t-cells unresponsive to interleukin-1, and unable to produce the t-cell growth factor il-2. cortisol downregulates the expression of the il2 receptor il-2r on the surface of the helper t-cell which is necessary to induce a th1 'cellular' immune response, thus favoring a shift towards th2 dominance and the release of the cytokines listed above which results in th2 dominance and favors the 'humoral' b-cell mediated antibody immune response. cortisol also has a negative-feedback effect on il-1. the way this negative feedback works is that an immune stressor causes peripheral immune cells to release il-1 and other cytokines such as il-6 and tnf-alpha. these cytokines stimulate the hypothalamus, causing it to release corticotropin-releasing hormone (crh). crh in turn stimulates the production of adrenocorticotropic hormone (acth) among other things in the adrenal gland, which (among other things) increases production of cortisol. cortisol then closes the loop as it inhibits tnf-alpha production in immune cells and makes them less responsive to il-1. through this system, as long as an immune stressor is small, the response will be regulated to the correct level. like a thermostat controlling a heater, the hypothalamus uses cortisol to turn off the heat once the production of cortisol matches the stress induced on the immune system. but in a severe infection or in a situation where the immune system is overly sensitized to an antigen (such as in allergic reactions) or there is a massive flood of antigens (as can happen with endotoxic bacteria) the correct set point might never be reached. also because of downregulation of th1 immunity by cortisol and other signaling molecules, certain types of infection, (notably mycobacterium tuberculosis) can trick the body into getting locked in the wrong mode of attack, using an antibody-mediated humoral response when a cellular response is needed. lymphocytes include the b-cell lymphocytes that are the antibody-producing cells of the body, and are thus the main agents of humoral immunity. a larger number of lymphocytes in the lymph nodes, bone marrow, and skin means the body is increasing its humoral immune response. b-cell lymphocytes release antibodies into the bloodstream. these antibodies lower infection through three main pathways: neutralization, opsonization, and complement activation. antibodies neutralize pathogens by binding to surface adhering proteins, keeping pathogens from binding to host cells. in opsonization, antibodies bind to the pathogen and create a target for phagocytic immune cells to find and latch onto, allowing them to destroy the pathogen more easily. finally antibodies can also activate complement molecules which can combine in various ways to promote opsonization or even act directly to lyse a bacteria. there are many different kinds of antibody and their production is highly complex, involving several types of lymphocyte, but in general lymphocytes and other antibody regulating and producing cells will migrate to the lymph nodes to aid in the release of these antibodies into the bloodstream. rapid administration of corticosterone (the endogenous type i and type ii receptor agonist) or ru28362 (a specific type ii receptor agonist) to adrenalectomized animals induced changes in leukocyte distribution. on the other side of things, there are natural killer cells; these cells have the ability to take down larger in size threats like bacteria, parasites, and tumor cells. a separate study found that cortisol effectively disarmed natural killer cells, downregulating the expression of their natural cytotoxicity receptors. interestingly, prolactin has the opposite effect. it increases the expression of cytotoxicity receptors on natural killer cells, increasing their firepower. cortisol stimulates many copper enzymes (often to 50% of their total potential), including lysyl oxidase, an enzyme that cross-links collagen and elastin. especially valuable for immune response is cortisol's stimulation of the superoxide dismutase, since this copper enzyme is almost certainly used by the body to permit superoxides to poison bacteria. other effects glucose cortisol counteracts insulin, contributes to hyperglycemia by stimulating gluconeogenesis and inhibits the peripheral use of glucose (insulin resistance) by decreasing the translocation of glucose transporters (especially glut4) to the cell membrane. cortisol also increases glycogen synthesis (glycogenesis) in the liver, storing glucose in easily accessible form. the permissive effect of cortisol on insulin action in liver glycogenesis is observed in hepatocyte culture in the laboratory, although the mechanism for this is unknown. bone and collagen cortisol reduces bone formation, favoring long-term development of osteoporosis (progressive bone disease). the mechanism behind this is two-fold: cortisol stimulates the production of rankl by osteoblasts which stimulates, through binding to rank receptors, the activity of osteoclasts – cells responsible for calcium resorption from bone – and also inhibits the production of osteoprotegerin (opg) which acts as a decoy receptor and captures some rankl before it can activate the osteoclasts through rank. in other words, when rankl binds to opg, no response occurs as opposed to the binding to rank which leads to the activation of osteoclasts. it transports potassium out of cells in exchange for an equal number of sodium ions (see above). this can trigger the hyperkalemia of metabolic shock from surgery. cortisol also reduces calcium absorption in the intestine. cortisol down-regulates the synthesis of collagen. amino acid cortisol raises the free amino acids in the serum by inhibiting collagen formation, decreasing amino acid uptake by muscle, and inhibiting protein synthesis. cortisol (as opticortinol) may inversely inhibit iga precursor cells in the intestines of calves. cortisol also inhibits iga in serum, as it does igm; however, it is not shown to inhibit ige. electrolyte balance cortisol decreases glomerular filtration rate, and renal plasma flow from the kidneys thus increasing phosphate excretion, as well as increasing sodium and water retention and potassium excretion by acting on mineralocorticoid receptors. it also increases sodium and water absorption and potassium excretion in the intestines. sodium cortisol promotes sodium absorption through the small intestine of mammals. sodium depletion, however, does not affect cortisol levels so cortisol cannot be used to regulate serum sodium. cortisol's original purpose may have been sodium transport. this hypothesis is supported by the fact that freshwater fish use cortisol to stimulate sodium inward, while saltwater fish have a cortisol-based system for expelling excess sodium. potassium a sodium load augments the intense potassium excretion by cortisol. corticosterone is comparable to cortisol in this case. for potassium to move out of the cell, cortisol moves an equal number of sodium ions into the cell. this should make ph regulation much easier (unlike the normal potassium-deficiency situation, in which two sodium ions move in for each three potassium ions that move out—closer to the deoxycorticosterone effect). stomach and kidneys cortisol stimulates gastric-acid secretion. cortisol's only direct effect on the hydrogen-ion excretion of the kidneys is to stimulate the excretion of ammonium ions by deactivating the renal glutaminase enzyme. memory cortisol works with adrenaline (epinephrine) to create memories of short-term emotional events; this is the proposed mechanism for storage of flash bulb memories, and may originate as a means to remember what to avoid in the future. however, long-term exposure to cortisol damages cells in the hippocampus; this damage results in impaired learning. diurnal cycles change in plasma cortisol cycle (mcg/dl) over 24 hours diurnal cycles of cortisol levels are found in humans. stress sustained stress can lead to high levels of circulating cortisol (regarded as one of the more important of the several "stress hormones"). effects during pregnancy during human pregnancy, increased fetal production of cortisol between weeks 30 and 32 initiates production of fetal lung pulmonary surfactant to promote maturation of the lungs. in fetal lambs, glucocorticoids (principally cortisol) increase after about day 130, with lung surfactant increasing greatly, in response, by about day 135, and although lamb fetal cortisol is mostly of maternal origin during the first 122 days, 88% or more is of fetal origin by day 136 of gestation. although the timing of fetal cortisol concentration elevation in sheep may vary somewhat, it averages about 11.8 days before the onset of labor. in several livestock species (e.g. cattle, sheep, goats, and pigs), the surge of fetal cortisol late in gestation triggers the onset of parturition by removing the progesterone block of cervical dilation and myometrial contraction. the