Cortisol is produced in the human body by the adrenal gland in the zona fasciculata, the second of three layers comprising the adrenal cortex. The cortex forms the outer "bark" of each adrenal gland, situated atop the kidneys. The release of cortisol is controlled by the hypothalamus, a part of the brain. The secretion of corticotropin-releasing hormone (CRH) by the hypothalamus triggers cells in the neighboring anterior pituitary to secrete another hormone, adrenocorticotropic hormone (ACTH), into the vascular system, through which blood carries it to the adrenal cortex.
Cortisol for injection
Main functions in the body
In the fasting state, cortisol stimulates gluconeogenesis (formation, in the liver, of glucose from certain amino acids, glycerol, lactate, and/or propionate), and it activates anti-stress and anti-inflammatory pathways.
It downregulates the Interleukin-2 receptor (IL-2R) on "Helper" (CD4+) T-cells. This results in the inability of Interleukin-2 to upregulate the Th2 (Humoral) immune response and results in a Th1 (Cellular) immune dominance. This results in a decrease in B-cellantibody production. Cortisol prevents the release of substances in the body that cause inflammation. This is why cortisol is used to treat conditions resulting from overactivity of the B-cell-mediated antibody response such as inflammatory and rheumatoid diseases, and allergies. Low-potency hydrocortisone, available over the counter in some countries, is used to treat skin problems such as rashes, eczema, and others.
Cortisol plays an important role in glycogenolysis, the breaking down of glycogen to glucose-1-phosphate and glucose, in liver and muscle tissue. Glycogenolysis is stimulated by epinephrine and/or norepinephrine, however cortisol facilitates the activation of glycogen phosphorylase, which is essential for the effects of epinephrine on glycogenolysis.
Elevated levels of cortisol, if prolonged, can lead to proteolysis and muscle wasting.
Several studies have shown a lipolytic (breakdown of fat) effect of cortisol, although, under some conditions, cortisol may somewhat suppress lipolysis.
Another function is to decrease bone formation.
During human pregnancy, increased fetal production of cortisol between weeks 30 and 32 initiates production of fetal lung 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 percent 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. the cow, sheep, goat and pig), 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 mechanisms yielding this effect on progesterone differ among species. In the sheep, where progesterone sufficient for maintaining pregnancy is produced by the placenta after about day 70 of gestation, the pre-partum fetal cortisol surge induces placental enzymatic conversion of progesterone to estrogen. (The elevated level of estrogen stimulates prostaglandin secretion and oxytocin receptor development.) In the pregnant cow, where progesterone maintaining pregnancy is provided by the corpus luteum, luteolysis is induced by endometrial release of prostaglandin F2alpha, in response to fetal cortisol (and estrogen).
Exposure of fetuses to cortisol during gestation can have a variety of developmental outcomes, including alterations in prenatal and postnatal growth patterns. In marmosets, a species of New World primates, pregnant females have varying levels of cortisol during gestation, both within and between females. Mustoe et al. (2012) showed that infants born to mothers with high gestational cortisol during the first trimester of pregnancy had lower rates of growth in body mass indices (BMI) than infants born to mothers with low gestational cortisol (approximately 20% lower). However, postnatal growth rates in these high-cortisol infants was more rapid than low-cortisol infants later in postnatal periods, and complete catch-up in growth had occurred by 540 days of age. These results suggest that gestational exposure to cortisol in fetuses has important potential fetal programming effects on both pre- and post-natal growth in primates.
Cortisol is released in response to stress, sparing available glucose for the brain, generating new energy from stored reserves, and diverting energy from low-priority activities (such as the immune system) in order to survive immediate threats or prepare for the exertion of rising to a new day. However, prolonged cortisol secretion (which may be due to chronic stress or the excessive secretion seen in Cushing's syndrome) results in significant physiological changes (proper source needed).
Cortisol and Separation
Cortisol and Separation Cortisol has also been linked to various types of separation. One widely studied form of separation is maternal separation. Following maternal separation, there is a significant increase in cortisol among both the mother and the infant. These changes are due to dysfunctions in the Hypothalamic-pituitary-adrenal (HPA) axis during a critical period in childhood. One study found that cortisol levels significantly decreased in peer-reared Rhesus monkeys in comparison to mother-reared monkeys at the age of two years. This difference was significant at the mark of two years, and remained significant when tested again at three and a half years. This study marks the importance of maternal care, showing that despite being raised by a large support group, Rhesus monkeys experience high increases in cortisol when raised without their mother.
These effects of maternal separation on cortisol also continue much later in life. One study which examined mid-aged men and women and found that separation lasting 1 or more years during childhood is associated with decreased levels of cortisol secretion, possibly symbolizing a diminished activity of the HPA axis. Another study examined adults who were put in to foster care during World War II. Those separated from both of their parents had higher levels of cortisol in comparison to those who were not separated. These effects were seen more than 60 years after the childhood separation had occurred. This study also found that the length of separation did not affect hormonal responses. .
These studies mark the importance of maternal care and its effect on cortisol levels not only during childhood separations, but also cortisol levels later in life. More research is needed in this area to be sure of the definite cause of different HPA axis functioning later in life. Also, future research is needed to be sure there is indeed a critical period for maternal separation and its resulting decrease in cortisol. .
Aside from maternal separation, studies have found that increases in cortisol levels are also associated with romantic partner separations. These increases in cortisol were more commonly found when the partner who was left for a period of 4 to 6 days has a high attachment anxiety. This could be due to increased stress when their partner was away. But, further evidence is needed to identify the relationship between romantic separation and cortisol. .
In laboratory rats, cortisol-induced collagen loss in the skin is ten times greater than in any other tissue.
Cortisol raises the free amino acids in the serum. It does this 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.
Gastric and renal secretion
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. Net chloride secretion in the intestines is inversely decreased by cortisol in vitro (methylprednisolone).
Cortisol inhibits sodium loss 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 utilize cortisol to stimulate sodium inward, while saltwater fish have a cortisol-based system for expelling excess sodium.
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). Nevertheless, cortisol consistently causes serum alkalosis; in a deficiency, serum pH does not change. The purpose of this may be to reduce serum pH to an optimum value for some immune enzymes during infection, when cortisol declines. Potassium is also blocked from loss in the kidneys by a decline in cortisol (9 alpha fluorohydrocortisone).
Cortisol acts as antidiuretic hormone, controlling one-half of intestinal diuresis; it has also been shown to control kidney diuresis in dogs. The decline in water excretion following a decline in cortisol (dexamethasone) in dogs is probably due to inverse stimulation of antidiuretic hormone (ADH or arginine vasopressin), which is not overridden by water loading. Humans and other animals also use this mechanism.
Cortisol stimulates many copper enzymes (often to 50% of their total potential), probably to increase copper availability for immune purposes.:337 This includes lysyl oxidase, an enzyme that cross-links collagen and elastin.:334 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. Cortisol causes an inverse four- or fivefold decrease of metallothionein (a copper storage protein) in mice; however, rodents do not synthesize cortisol themselves. This may be to furnish more copper for ceruloplasmin synthesis or to release free copper. Cortisol has an opposite effect on aminoisobuteric acid than on the other amino acids. If alpha-aminoisobuteric acid is used to transport copper through the cell wall, this anomaly might be explained.
Cortisol can weaken the activity of the immune system. Cortisol prevents proliferation of T-cells by rendering the interleukin-2 producer T-cells unresponsive to interleukin-1 (IL-1), and unable to produce the T-cell growth factor. Cortisol also has a negative-feedback effect on interleukin-1. IL-1 must be especially useful in combating some diseases; however, endotoxic bacteria have gained an advantage by forcing the hypothalamus to increase cortisol levels (forcing the secretion of CRH hormone, thus antagonizing IL-1). The suppressor cells are not affected by glucosteroid response-modifying factor (GRMF), so the effective setpoint for the immune cells may be even higher than the setpoint for physiological processes (reflecting leukocyte redistribution to lymph nodes, bone marrow, and skin). 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. Natural killer cells are not affected by cortisol.
Cortisol reduces bone formation, favoring long-term development of osteoporosis. 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 works with epinephrine (adrenaline) 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. Furthermore, it has been shown that cortisol inhibits memory retrieval of already stored information.
Shuts down the reproductive system, resulting in an increased chance of miscarriage and (in some cases) temporary infertility. Fertility returns after cortisol levels return to normal.
Has anti-inflammatory properties, reducing histamine secretion and stabilizing lysosomal membranes. Stabilization of lysosomal membranes prevents their rupture, preventing damage to healthy tissues
In addition to cortisol's effects in binding to the glucocorticoid receptor, because of its molecular similarity to aldosterone it also binds to the mineralocorticoid receptor. Aldosterone and cortisol have a similar affinity for the mineralocorticoid receptor; however, glucocorticoids circulate at roughly 100 times the level of mineralocorticoids. An enzyme exists in mineralocorticoid target tissues to prevent overstimulation by glucocorticoids and allow selective mineralocorticoid action. This enzyme—11-beta hydroxysteroid dehydrogenase type II (Protein:HSD11B2)—catalyzes the deactivation of glucocorticoids to 11-dehydro metabolites
There are potential links between cortisol, appetite, and obesity.
Normal values indicated in the following tables pertain to humans (Normals vary among species). Measured cortisol levels, and therefore reference ranges, depend on the analytical method used and factors such as age and sex. Test results should, therefore, always be interpreted using the reference range from the laboratory that produced the result.
Diurnal cycles of cortisol levels are found in several animal species, including humans. In species that exhibit such cycles, different timing of diurnal maxima and minima has been observed, not only in different species but also, in some cases, within the same species.
In humans, the amount of cortisol present in the blood undergoes diurnal variation; the level peaks in the early morning (approximately 8 am) and reaches its lowest level at about midnight-4 am, or three to five hours after the onset of sleep. Information about the light/dark cycle is transmitted from the retina to the paired suprachiasmatic nuclei in the hypothalamus. This pattern is not present at birth; estimates of when it begins vary from two weeks to nine months of age.
The primary control of cortisol is the pituitary gland peptide, adrenocorticotropic hormone (ACTH). ACTH probably controls cortisol by controlling the movement of calcium into the cortisol-secreting target cells. ACTH is in turn controlled by the hypothalamic peptide corticotropin-releasing hormone (CRH), which is under nervous control. CRH acts synergistically with arginine vasopressin, angiotensin II, and epinephrine. (In swine, which do not produce arginine vasopressin, lysine vasopressin acts synergistically with CRH.) When activated macrophages start to secrete interleukin-1 (IL-1), which synergistically with CRH increases ACTH,T-cells also secrete glucosteroid response modifying factor (GRMF or GAF) as well as IL-1; both increase the amount of cortisol required to inhibit almost all the immune cells. Immune cells then assume their own regulation, but at a higher cortisol setpoint. The increase in cortisol in diarrheic calves is minimal over healthy calves, however, and falls over time. The cells do not lose all their fight-or-flight override because of interleukin-1's synergism with CRH. Cortisol even has a negative feedback effect on interleukin-1—especially useful to treat diseases that force the hypothalamus to secrete too much CRH, such as those caused by endotoxic bacteria. The suppressor immune cells are not affected by GRMF, so the immune cells' effective setpoint may be even higher than the setpoint for physiological processes. GRMF (known as GAF in this reference) affects primarily the liver (rather than the kidneys) for some physiological processes.
High-potassium media (which stimulates aldosterone secretion in vitro) also stimulate cortisol secretion from the fasciculata zone of canine adrenals  — unlike corticosterone, upon which potassium has no effect. Potassium loading also increases ACTH and cortisol in humans. This is probably the reason why potassium deficiency causes cortisol to decline (as mentioned) and causes a decrease in conversion of 11-deoxycortisol to cortisol. This may also have a role in rheumatoid-arthritis pain; cell potassium is always low in RA.
Factors generally reducing cortisol levels
Magnesium supplementation decreases serum cortisol levels after aerobic exercise, but not after resistance training.
Omega-3 fatty acids have a dose-dependent effect in slightly reducing cortisol release influenced by mental stress, suppressing the synthesis of interleukin-1 and -6 and enhancing the synthesis of interleukin-2; the former promotes higher CRH release. Omega-6 fatty acids, on the other hand, have an inverse effect on interleukin synthesis.
Intense (high VO2 max) or prolonged physical exercise stimulates cortisol release to increase gluconeogenesis and maintain blood glucose. Proper nutrition and high-level conditioning can help stabilize cortisol release.
The Val/Val variation of the BDNF gene in men and the Val/Met variation in women are associated with increased salivary cortisol in a stressful situation.
A 2010 study has found that serum cortisol predicts increased cardiovascular mortality in patients with acute coronary syndrome.
Hydrocortisone is the pharmaceutical term for cortisol used in oral administration, intravenous injection, or topical application. It is used as an immunosuppressive drug, given by injection in the treatment of severe allergic reactions such as anaphylaxis and angioedema, in place of prednisolone in patients needing steroid treatment but unable take oral medication, and perioperatively in patients on long-term steroid treatment to prevent Addisonian crisis. It may be used topically for allergic rashes, eczema, psoriasis, and certain other inflammatory skin conditions. It may also be injected into inflamed joints resulting from diseases such as gout. Fluticasone propionate is a corticosteroid used in nasal sprays and asthma inhalers.
Topical hydrocortisone creams and ointments are available in most countries without prescription in strengths ranging from 0.05% to 2.5% (depending on local regulations) with stronger forms available by prescription only. Covering the skin after application increases the absorption and effect. Such enhancement is sometimes prescribed, but otherwise should be avoided to prevent overdose and systemic impact.
Advertising for the dietary supplement CortiSlim originally (and falsely) claimed that it contributed to weight loss by blocking cortisol. The manufacturer was fined $12 million by the Federal Trade Commission in 2007 for false advertising and no longer claims in their marketing that CortiSlim is a cortisol antagonist.
Cortisol is synthesized from cholesterol. Synthesis takes place in the zona fasciculata of the adrenal cortex. (The name cortisol is derived from cortex.) While the adrenal cortex also produces aldosterone (in the zona glomerulosa) and some sex hormones (in the zona reticularis), cortisol is its main secretion in humans and several other species. (However, in cattle, corticosterone levels may approach or exceed. cortisol levels.). The medulla of the adrenal gland lies under the cortex, mainly secreting the catecholamines adrenaline (epinephrine) and noradrenaline (norepinephrine) under sympathetic stimulation.
11-beta HSD1 utilizes the cofactor NADPH to convert biologically inert cortisone to biologically active cortisol
11-beta HSD2 utilizes the cofactor NAD+ to convert cortisol to cortisone
Overall, the net effect is that 11-beta HSD1 serves to increase the local concentrations of biologically active cortisol in a given tissue; 11-beta HSD2 serves to decrease local concentrations of biologically active cortisol.
Cortisol is also metabolized into 5-alpha tetrahydrocortisol (5-alpha THF) and 5-beta tetrahydrocortisol (5-beta THF), reactions for which 5-alpha reductase and 5-beta reductase are the rate-limiting factors, respectively. 5-Beta reductase is also the rate-limiting factor in the conversion of cortisone to tetrahydrocortisone (THE).
By measuring salivary cortisol, researchers have found a decrease in cortisol concentration in leadership roles as compared to non-leadership roles. The results were independent of differences in education and income.
Cortisol, as well as other glucocorticoids, have been used as biomarkers of psychological stress.
Cohen et al. found that "lower socioeconomic status and being black were associated with higher evening levels of cortisol. These relationships were independent of one another and socioeconomic status associations with cortisol were similar across racial categories."
^Djurhuus CB, Gravholt CH, Nielsen S, Mengel A, Christiansen JS, Schmitz OE, Møller N (July 2002). "Effects of cortisol on lipolysis and regional interstitial glycerol levels in humans". Am. J. Physiol. Endocrinol. Metab.283 (1): E172–7. doi:10.1152/ajpendo.00544.2001. PMID12067858.Cite uses deprecated parameters (help)
^Mescher EJ, Platzker AC, Ballard PL, Kitterman JA, Clements JA, Tooley WH (December 1975). "Ontogeny of tracheal fluid, pulmonary surfactant, and plasma corticoids in the fetal lamb". J Appl Physiol39 (6): 1017–21. PMID2573.Cite uses deprecated parameters (help)
^Hennessy DP, Coghlan JP, Hardy KJ, Scoggins BA, Wintour EM (October 1982). "The origin of cortisol in the blood of fetal sheep". J. Endocrinol.95 (1): 71–9. doi:10.1677/joe.0.0950071. PMID7130892.Cite uses deprecated parameters (help)
^Magyar DM, Fridshal D, Elsner CW, Glatz T, Eliot J, Klein AH, Lowe KC, Buster JE, Nathanielsz PW (July 1980). "Time-trend analysis of plasma cortisol concentrations in the fetal sheep in relation to parturition". Endocrinology107 (1): 155–9. doi:10.1210/endo-107-1-155. PMID7379742.Cite uses deprecated parameters (help)
^Ricketts AP, Flint AP (August 1980). "Onset of synthesis of progesterone by ovine placenta". J. Endocrinol.86 (2): 337–47. doi:10.1677/joe.0.0860337. PMID6933207.Cite uses deprecated parameters (help)
^Al-Gubory KH, Solari A, Mirman B (1999). "Effects of luteectomy on the maintenance of pregnancy, circulating progesterone concentrations and lambing performance in sheep". Reprod. Fertil. Dev.11 (6): 317–22. doi:10.1071/RD99079. PMID10972299.
^Jainudeen MR, Hafez ESE (2000). "Gestation, prenatal physiology, and parturition". In Hafez ESE, Hafez B. Reproduction in farm animals. Hagerstwon, MD: Lippincott Williams & Wilkins. pp. 140–155. ISBN0-683-30577-8.
^X. Feng, L. Wang , Yang S., D. Qin, J. Wang , C. Li, L. Lv, Y. Ma, X. Hu (November 2012). "Maternal separation produces lasting changes in cortisol and behavior in rhesus monkeys". PNAS34: 14312–14317. doi:10.1073/pnas.1010943108.Cite uses deprecated parameters (help)
^ abM. Kumari, J. Head, M Bartley, S. Stansfeld, M. Kivimaki (July 2012). "Maternal separation in childhood and diurnal cortisol patterns in mid-life: findings from the Whitehall II study". Psychological Medicine: 633 – 643. doi:10.1017/S0033291712001353.Cite uses deprecated parameters (help)
^A. Pesonen, K Raikkonwn, K. Feldtm K Heinonen, C. Osmond, D. Philips, D. Barker, J. Eriksson, E. Kajantie (April 2010). "Childhood separation experience predicts HPA axis hormonal responses in late adulthood: A natural experience of World War II". Psychoneuroendocrinology35: 785 – 767. doi:10.1016/j.psyneuen.2009.10.017.Cite uses deprecated parameters (help)
^L. M. Diamond, A. M. Hicks, K. D. Otter-Henderson (November 2008). "Every time you go away: Changes in affect, behavior, and physiology associated with travel-related separations from romantic partners.". Journal of Personality and Social Psychology95: 385 – 493. doi:10.1037/0022-35126.96.36.1995.Cite uses deprecated parameters (help)
^King MB (2005). Lange Q & A. New York: McGraw-Hill, Medical Pub. Division. ISBN0-07-144578-1.
^Piroli, G. G.; Grillo, C. A.; Reznikov, L. R.; Adams, S.; McEwen, B. S.; Charron, M. J.; Reagan, L. P. (2007). "Corticosterone Impairs Insulin-Stimulated Translocation of GLUT4 in the Rat Hippocampus". Neuroendocrinology85 (2): 71–80. doi:10.1159/000101694. PMID17426391. edit
^Houck JC, Sharma VK, Patel YM, Gladner JA (October 1968). "Induction of collagenolytic and proteolytic activities by anti-inflammatory drugs in the skin and fibroblast". Biochem. Pharmacol.17 (10): 2081–90. doi:10.1016/0006-2952(68)90182-2. PMID4301453.Cite uses deprecated parameters (help)
^Manchester, KL (1964). "Sites of Hormonal Regulation of Protein Metabolism". In Allison, NH & Munro JB. Mammalian Protein Metabolism. New York: Academic Press. p. 229? 273?.
^Husband AJ, Brandon MR, Lascelles AK (October 1973). "The effect of corticosteroid on absorption and endogenous production of immunoglobulins in calves". Aust J Exp Biol Med Sci51 (5): 707–10. doi:10.1038/icb.1973.67. PMID4207041.Cite uses deprecated parameters (help)
^Posey WC, Nelson HS, Branch B, Pearlman DS (December 1978). "The effects of acute corticosteroid therapy for asthma on serum immunoglobulin levels". The Journal of Allergy and Clinical Immunology62 (6): 340–8. doi:10.1016/0091-6749(78)90134-3. PMID712020.Cite uses deprecated parameters (help)
^Soffer LJ, Dorfman RI, Gabrilove JL (1961). The Human Adrenal Gland. Philadelphia: Lea & Febiger.
^Kokshchuk GI, Pakhmurnyi BA (December 1979). "Role of Glucocorticoids in Regulation of the Acid-Excreting Function of the Kidneys". Fiziol. Z H SSR I.M.I.M. Sechenova65 (6): 340–8. doi:10.1016/0091-6749(78)90134-3. PMID712020.Cite uses deprecated parameters (help)
^Tai YH, Decker RA, Marnane WG, Charney AN, Donowitz M (May 1981). "Effects of methylprednisolone on electrolyte transport by in vitro rat ileum". Am. J. Physiol.240 (5): G365–70. PMID6112881.Cite uses deprecated parameters (help)
^ abSandle GI, Keir MJ, Record CO (1981). "The effect of hydrocortisone on the transport of water, sodium, and glucose in the jejunum. Perfusion studies in normal subjects and patients with coeliac disease". Scand. J. Gastroenterol.16 (5): 667–71. doi:10.3109/00365528109182028. PMID7323700.
^Mason PA, Fraser R, Morton JJ, Semple PF, Wilson A (August 1977). "The effect of sodium deprivation and of angiotensin II infusion on the peripheral plasma concentrations of 18-hydroxycorticosterone, aldosterone and other corticosteroids in man". J. Steroid Biochem.8 (8): 799–804. doi:10.1016/0022-4731(77)90086-3. PMID592808.Cite uses deprecated parameters (help)
^Gorbman A, Dickhoff WW, Vigna SR, Clark NB, Muller AF (1983). Comparative endocrinology. New York: Wiley. ISBN0-471-06266-9.
^ abKnight RP, Kornfeld DS, Glaser GH, Bondy PK (February 1955). "Effects of intravenous hydrocortisone on electrolytes of serum and urine in man". J. Clin. Endocrinol. Metab.15 (2): 176–81. doi:10.1210/jcem-15-2-176. PMID13233328.Cite uses deprecated parameters (help)
^Barger AC, Berlin RD, Tulenko JF (June 1958). "Infusion of aldosterone, 9-alpha-fluorohydrocortisone and antidiuretic hormone into the renal artery of normal and adrenalectomized, unanesthetized dogs: effect on electrolyte and water excretion". Endocrinology62 (6): 804–15. doi:10.1210/endo-62-6-804. PMID13548099.Cite uses deprecated parameters (help)
^Chambers JW, Georg RH, Bass AD (July 1965). "Effect of hydrocortisone and insulin on uptake of alpha-aminoisobutyric acid by isolated perfused rat liver". Mol. Pharmacol.1 (1): 66–76. PMID5835080.Cite uses deprecated parameters (help)
^Palacios R, Sugawara I (January 1982). "Hydrocortisone abrogates proliferation of T cells in autologous mixed lymphocyte reaction by rendering the interleukin-2 Producer T cells unresponsive to interleukin-1 and unable to synthesize the T-cell growth factor". Scand. Journal of Immunology15 (1): 25–31. doi:10.1111/j.1365-3083.1982.tb00618.x. PMID6461917.Cite uses deprecated parameters (help)
^ abcBesedovsky HO, Del Rey A, Sorkin E (1986). "Integration of Activated Immune Cell Products in Immune Endocrine Feedback Circuits". In Oppenheim JJ, Jacobs DM. Leukocytes and Host Defense. Progress in Leukocyte Biology 5. New York: Alan R. Liss. p. 200.
^ abcFairchild SS, Shannon K, Kwan E, Mishell RI (February 1984). "T cell-derived glucosteroid response-modifying factor (GRMFT): a unique lymphokine made by normal T lymphocytes and a T cell hybridoma". Journal of Immunology132 (2): 821–7. PMID6228602.Cite uses deprecated parameters (help)
^Onsrud M, Thorsby E (1981). "Influence of in vivo hydrocortisone on some human blood lymphocyte subpopulations. I. Effect on natural killer cell activity". Scand. Journal of Immunology13 (6): 573–9. doi:10.1111/j.1365-3083.1981.tb00171.x. PMID7313552.
^Deutsch E (April 1978). "[Pathogenesis of thrombocytopenia. 2. Distribution disorders, pseudo-thrombocytopenias]". Fortschr. Med. (in German) 96 (14): 761–2. PMID346457.Cite uses deprecated parameters (help)
^ abcdDerived from molar values using molar mass of 362 g/mol
^ abConverted from µg/24h, using molar mass of 362.460 g/mol
^ abGörges r, K. G.; Knappe, G.; Gerl, H.; Ventz, M.; Stahl, F. (1999). "Diagnosis of Cushing's syndrome: Re-evaluation of midnight plasma cortisol vs urinary free cortisol and low-dose dexamethasone suppression test in a large patient group". Journal of endocrinological investigation22 (4): 241–249. PMID10342356. edit
^ abConverted from nmol/24h, using molar mass of 362.460 g/mol
^ abFulkerson WJ, Tang BY (April 1979). "Ultradian and circadian rhythms in the plasma concentration of cortisol in sheep". J. Endocrinol.81 (1): 135–41. doi:10.1677/joe.0.0810135. PMID469453.Cite uses deprecated parameters (help)
^Mesbah S, Brudieux R (June 1982). "Diurnal variation of plasma concentrations of cortisol, aldosterone and electrolytes in the ram". Horm. Metab. Res.14 (6): 320–3. doi:10.1055/s-2007-1019005. PMID6889565.Cite uses deprecated parameters (help)
^Simonetta G, Walker DW, McMillen IC (March 1991). "Effect of feeding on the diurnal rhythm of plasma cortisol and adrenocorticotrophic hormone concentrations in the pregnant ewe and sheep fetus". Exp. Physiol.76 (2): 219–29. PMID1647800.Cite uses deprecated parameters (help)
^Plotsky PM, Otto S, Sapolsky RM (September 1986). "Inhibition of immunoreactive corticotropin-releasing factor secretion into the hypophysial-portal circulation by delayed glucocorticoid feedback". Endocrinology119 (3): 1126–30. doi:10.1210/endo-119-3-1126. PMID3015567.Cite uses deprecated parameters (help)
^Minton JE, Parsons KM (March 1993). "Adrenocorticotropic hormone and cortisol response to corticotropin-releasing factor and lysine vasopressin in pigs". J. Anim. Sci.71 (3): 724–9. PMID8385088.Cite uses deprecated parameters (help)
^Dvorak M (1971). "Plasma 17-Hydroxycorticosteroid Levels in Healthy and Diarrheic Calves". British Veterinarian Journal127: 372.
^Stith RD, McCallum RE (1986). "General effect of endotoxin on glucocorticoid receptors in mammalian tissues". Circ. Shock18 (4): 301–9. PMID3084123.
^Mikosha AS, Pushkarov IS, Chelnakova IS, Remennikov GYA (1991). "Potassium Aided Regulation of Hormone Biosynthesis in Adrenals of Guinea Pigs Under Action of Dihydropyridines: Possible Mechanisms of Changes in Steroidogenesis Induced by 1,4, Dihydropyridines in Dispersed Adrenocorticytes". Fiziol. [Kiev]37: 60.
^Mendelsohn FA, Mackie C (July 1975). "Relation of intracellular K+ and steroidogenesis in isolated adrenal zona glomerulosa and fasciculata cells". Clin Sci Mol Med49 (1): 13–26. PMID168026.Cite uses deprecated parameters (help)
^Ueda Y, Honda M, Tsuchiya M, Watanabe H, Izumi Y, Shiratsuchi T, Inoue T, Hatano M (April 1982). "Response of plasma ACTH and adrenocortical hormones to potassium loading in essential hypertension". Jpn. Circ. J.46 (4): 317–22. doi:10.1253/jcj.46.317. PMID6283190.Cite uses deprecated parameters (help)
^Bauman K, Muller J (1972). "Effect of potassium on the final status of aldosterone biosynthesis in the rat. I 18-hydroxylation and 18hydroxy dehydrogenation. II beta-hydroxylation". Acta Endocrin. Copenh.69: I 701–717, II 718–730.
^LaCelle PL, et al. (1964). "An investigation of total body potassium in patients with rheumatoid arthritis". Proceedings of the Annual Meeting of the American Rheumatism Association, Arthritis and Rheumatism7: 321.
^Golf, S. W.; Happel, O.; Graef, V.; Seim, K. E. (November 1984). "Plasma aldosterone, cortisol and electrolyte concentrations in physical exercise after magnesium supplementation". Journal of clinical chemistry and clinical biochemistry. Zeitschrift fur klinische Chemie und klinische Biochemie22 (11): 717–721. ISSN0340-076X. PMID6527092. edit
^Golf, S. W.; Bender, S.; Grüttner, J. (September 1998). "On the significance of magnesium in extreme physical stress". Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy. 12 2 (2suppl): 197–202. doi:10.1023/A:1007708918683. ISSN0920-3206. PMID9794094. edit
^Field, T.; Hernandez-Reif, M.; Diego, M.; Schanberg, S.; Kuhn, C. (Oct 2005). "Cortisol decreases and serotonin and dopamine increase following massage therapy". The International journal of neuroscience115 (10): 1397–1413. doi:10.1080/00207450590956459. ISSN0020-7454. PMID16162447. edit
^Steptoe A, Gibson EL, Vuononvirta R, Williams ED, Hamer M, Rycroft JA, Erusalimsky JD, Wardle J (2007). "The effects of tea on psychophysiological stress responsivity and post-stress recovery: a randomised double-blind trial". Psychopharmacology190 (1): 81–89. doi:10.1007/s00213-006-0573-2. PMID17013636. edit
^Quiroga MC, Bongard S, Kreutz G (July 2009). "Emotional and Neurohumoral Responses to Dancing Tango Argentino: The Effects of Music and Partner". Music and Medicine1 (1): 14–21. doi:10.1177/1943862109335064.Cite uses deprecated parameters (help)
^Leproult R, Copinschi G, Buxton O, Van Cauter E (October 1997). "Sleep loss results in an elevation of cortisol levels the next evening". Sleep20 (10): 865–70. PMID9415946.Cite uses deprecated parameters (help)
^Robson PJ, Blannin AK, Walsh NP, Castell LM, Gleeson M (February 1999). "Effects of exercise intensity, duration and recovery on in vitro neutrophil function in male athletes". Int J Sports Med20 (2): 128–35. doi:10.1055/s-2007-971106. PMID10190775.Cite uses deprecated parameters (help)
^Kraemer WJ, Spiering BA, Volek JS, Martin GJ, Howard RL, Ratamess NA, Hatfield DL, Vingren JL, Ho JY, Fragala MS, Thomas GA, French DN, Anderson JM, Häkkinen K, Maresh CM (January 2009). "Recovery from a national collegiate athletic association division I football game: muscle damage and hormonal status". J Strength Cond Res23 (1): 2–10. doi:10.1519/JSC.0b013e31819306f2. PMID19077734.Cite uses deprecated parameters (help)
^Shalev, I.; Lerer, E.; Israel, S.; Uzefovsky, F.; Gritsenko, I.; Mankuta, D.; Ebstein, R. P.; Kaitz, M. (Apr 2009). "BDNF Val66Met polymorphism is associated with HPA axis reactivity to psychological stress characterized by genotype and gender interactions". Psychoneuroendocrinology34 (3): 382–388. doi:10.1016/j.psyneuen.2008.09.017. ISSN0306-4530. PMID18990498. edit
^Wingenfeld, K.; Schulz, M.; Damkroeger, A.; Rose, M.; Driessen, M. (Mar 2009). "Elevated diurnal salivary cortisol in nurses is associated with burnout but not with vital exhaustion". Psychoneuroendocrinology34 (8): 1144–1151. doi:10.1016/j.psyneuen.2009.02.015. ISSN0306-4530. PMID19321266.edit
^Smith JL, Gropper SAS, Groff JL (2009). Advanced nutrition and humanmetabolism. Belmont, CA: Wadsworth Cengage Learning. p. 247. ISBN0-495-11657-2.
^Moberg GP, Mench JA (2000). The biology of animal stress: basic principles and implications for animal welfare. Wallingford, Oxon, UK: CABI Pub. p. 377. ISBN0-85199-359-1.
^Kotwica G, Franczak A, Okrasa S, Koziorowski M, Kurowicka B (March 2002). "Effects of mating stimuli and oxytocin on plasma cortisol concentration in gilts". Reprod Biol2 (1): 25–37. PMID14666160.Cite uses deprecated parameters (help)
^Fichter MM, Pirke KM, Holsboer F (January 1986). "Weight loss causes neuroendocrine disturbances: experimental study in healthy starving subjects". Psychiatry Res17 (1): 61–72. doi:10.1016/0165-1781(86)90042-9. PMID3080766.Cite uses deprecated parameters (help)
^Terzolo, M.; Bovio, S.; Pia, A.; Conton, P. A.; Reimondo, G.; Dall'Asta, C.; Bemporad, D.; Angeli, A.; Opocher, G.; Mannelli, M.; Ambrosi, B.; Mantero, F. (2005). "Midnight serum cortisol as a marker of increased cardiovascular risk in patients with a clinically inapparent adrenal adenoma". European journal of endocrinology / European Federation of Endocrine Societies153 (2): 307–315. doi:10.1530/eje.1.01959. PMID16061838.edit
^Tomlinson JW, Walker EA, Bujalska IJ, Draper N, Lavery GG, Cooper MS, Hewison M, Stewart PM (2004). "11 -Hydroxysteroid Dehydrogenase Type 1: A Tissue-Specific Regulator of Glucocorticoid Response". Endocrine Reviews25 (5): 831–866. doi:10.1210/er.2003-0031. PMID15466942. edit
^Sherman, Gary (Oct 2012). "Leadership is associated with lower levels of stress". Jooa J. Lee, Amy JC Cuddy, Jonathan Renshon, Christopher Oveis, James J. Gross, and Jennifer S. Lerner. Proceedings of the National Academy of Sciences of the United States of America109 (44): 17903–17907. doi:10.1073/pnas.1207042109. PMID23012416.Cite uses deprecated parameters (help)
^Djuric, Zora; Bird, Chloe E.; Furumoto-Dawson, Alice; Rauscher, Garth H.; Ruffin IV, Mack T.; Stowe, Raymond P.; Tucker, Katherine L.; Masi, Christopher M. (13 October 2008). "Biomarkers of Psychological Stress in Health Disparities Research". The Open Biomarkers Journal1 (1): 7–19. doi:10.2174/1875318300801010007.Cite uses deprecated parameters (help)
^Cohen, S.; Schwartz, J. E.; Epel, E.; Kirschbaum, C.; Sidney, S.; Seeman, T. (2006). "Socioeconomic Status, Race, and Diurnal Cortisol Decline in the Coronary Artery Risk Development in Young Adults (CARDIA) Study". Psychosomatic Medicine68 (1): 41–50. doi:10.1097/01.psy.0000195967.51768.ea. PMID16449410.edit