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Not to be confused with cortisone, a metabolite from cortisol, with a similar name, genesis, and function.
Systematic (IUPAC) name
Clinical data
AHFS/ monograph
MedlinePlus a682206
Licence data US FDA:link
Legal status
  • AU: Pharmacist only
  • UK: POM
  • US: OTC for topical administration; Rx-only for oral tablets , rectal use and intravenous therapy
Routes Oral tablets, intravenous, topical, rectal
CAS number 50-23-7 YesY
ATC code A01AC03 A07EA02 C05AA01 D07AA02 H02AB09 S01BA02 S02BA01
PubChem CID 5754
DrugBank DB00741
ChemSpider 5551 YesY
KEGG D00088 YesY
ChEBI CHEBI:17650 YesY
Chemical data
Formula C21H30O5 
Molecular mass 362.460 g/mol
 N (what is this?)  (verify)

Cortisol is a steroid hormone, more specifically a glucocorticoid, which is produced by the zona fasciculata of the adrenal cortex.[1] It is released in response to stress and a low level of blood glucose.

Its functions are to increase blood sugar through gluconeogenesis, to suppress the immune system, and to aid the metabolism of fat, protein, and carbohydrate.[2] It also decreases bone formation.[3]

Hydrocortisone (INN, USAN, BAN) is a name for cortisol when it is used as a medication. Hydrocortisone is used to treat people who lack adequate naturally generated cortisol. It is on the World Health Organization's List of Essential Medicines needed in a basic health system.[4]

Main functions in the body[edit]

Metabolic response[edit]

In the early fasting state, cortisol stimulated gluconeogenesis (formation of glucose, in the liver, from certain amino acids, glycerol, lactate, and/or propionate), and activates anti-stress and anti-inflammatory pathways.[5] Cortisol (as well as epinephrine and/or norepinephrine) also plays an important, but indirect, role in liver and muscle glycogenolysis, the breaking down of glycogen to glucose-1-phosphate and glucose. This is done through its passive influence on glucagon. Additionally, Cortisol facilitates the activation of glycogen phosphorylase, which is necessary for epinephrine to have an effect on glycogenolysis.[6][7]

In the late fasting state, the function of cortisol changes slightly and actually increases glycogenesis. This response is a conservatory process that allows the liver to take up any glucose that is not being used by peripheral tissue and turn it into liver glycogen stores to be used incase the body moves into the starvation state.

Elevated levels of cortisol, if prolonged, can lead to proteolysis (breakdown of proteins) and muscle wasting.[8] Several studies have shown a lipolytic (breakdown of fat) effect of cortisol, although, under some conditions, cortisol may somewhat suppress lipolysis.[9]

Immune response[edit]

Cortisol prevents the release of substances in the body that cause inflammation. It is used to treat conditions resulting from over activity of the B-cell-mediated antibody response. Examples include inflammatory and rheumatoid diseases, as well as allergies. Low-potency hydrocortisone, available as a non-prescription medicine in some countries, is used to treat skin problems such as rashes, and eczema.

It inhibits production of interleukin (IL)-12, interferon (IFN)-gamma, IFN-alpha and tumor-necrosis-factor (TNF)-alpha by antigen-presenting cells (APCs) and T helper (Th)1 cells, but upregulates IL-4, IL-10, and IL-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.[10]

Additional Information[edit]

Another function of cortisol is to decrease bone formation.[3]

Production and release[edit]

Cortisol is produced in the human body by the adrenal gland in the zona fasciculata,[1] 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[11] triggers cells in the neighboring anterior pituitary to secrete another hormone, the adrenocorticotropic hormone (ACTH), into the vascular system, through which blood carries it to the adrenal cortex. ACTH stimulates the synthesis of cortisol, glucocorticoids, mineralocorticoids and dehydroepiandrosterone (DHEA).

Cortisol for injection

Normal levels[edit]

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.

Reference ranges for blood plasma content of free cortisol
Time Lower limit Upper limit Unit
09:00 am 140[12] 700[12] nmol/L
5[13] 25[13] μg/dL
Midnight 80[12] 350[12] nmol/L
2.9[13] 13[13] μg/dL

Using the molecular weight of 362.460 g/mole, the conversion factor from µg/dl to nmol/L is approximately 27.6; thus, 10 µg/dl is approximately equal to 276 nmol/L.

Reference ranges for urinalysis of free cortisol
Lower limit Upper limit Unit
28[14] or 30[15] 280[14] or 490[15] nmol/24h
10[16] or 11[17] 100[16] or 176[17] µg/24 h

Disorders of cortisol production[edit]

Disorders of cortisol production, and some consequent conditions, are as follows:

Effects during pregnancy[edit]

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,[18] 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.[19] Although the timing of fetal cortisol concentration elevation in sheep may vary somewhat, it averages about 11.8 days before the onset of labor.[20] 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,[21][22] 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).[23]

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.[24]

Other effects[edit]

Maternal separation[edit]

Changes in cortisol have been linked to various types of separation.

One widely studied form of separation is maternal separation. Following maternal separation, there is a significant decrease in cortisol in both the mother and the infant. These changes are caused by dysfunctions in the hypothalamic-pituitary-adrenal (HPA) axis during a critical period of infancy.

A study first published online on August 15, 2011 found:

In this study, we assessed the basal hair cortisol in rhesus monkeys after 1.5 and 3 years of normal social life following an early separation. These results showed that peer-reared monkeys had significantly lower basal hair cortisol levels than the mother-reared monkeys at both years examined. The plasma cortisol was assessed in the monkeys after 1.5 years of normal social life, and the results indicated that the peak in the peer-reared cortisol response to acute stressors was substantially delayed. In addition, after 3 years of normal social life, abnormal behavioral patterns were identified in the peer-reared monkeys. They showed decreases in locomotion and initiated sitting together, as well as increases in stereotypical behaviors compared with the mother-reared monkeys.[25]

This study shows the importance of maternal care. It showed that, despite being raised by a large peer support group, rhesus monkeys experience long-lasting hypocortisolism when raised without their mother.

These effects of maternal separation on cortisol also continue much later in life. A study which examined middle-aged men and women found that separation lasting one or more years during childhood is associated with a greater cortisol awakening response (CAR) upon daily awakening but also with a flatter diurnal slope in the subject's cortisol level. The decrease in the natural diurnal cortisol fluctuation may indicate a diminished activity of the HPA axis.[26]

Another study examined adults who were put in 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. .[27]

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.[26]

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.[28]

Cortisol is released in response to stress, sparing available glucose for the brain, generating new energy from stored reserves, and diverting energy from lower-priority activities (such as the immune system) in order to survive immediate threats or prepare for exertion. 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.[citation needed]

Immune system[edit]

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 (IL-2).[29] Cortisol also has a negative-feedback effect on interleukin-1.[30]

Though IL-1 is 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),[31] 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 affected by cortisol.[32]

Cortisol activates synthesis of IκB. IκB binds to transcription factor NFκB and inhibits its synthesis of pro-inflammatory cytokines (such as IL-1).

Bone metabolism[edit]

Cortisol reduces bone formation, favoring long-term development of osteoporosis (progressive bone disease). It transports potassium out of cells in exchange for an equal number of sodium ions (see above).[33] This can trigger the hyperkalemia of metabolic shock from surgery. Cortisol also reduces calcium absorption in the intestine.[34]


Collagen is a molecule that makes connective tissue. It is vital for structural support and is found in muscles, tendons, and joints, as well as throughout the entire body. Cortisol inhibits collagen.[35] Stress studies showed that in laboratory rats, cortisol-induced collagen loss in the skin is ten times greater than in any other tissue.[36]

Wound healing[edit]

Cortisol and the stress response have known deleterious effects on the immune system. High levels of perceived stress and increases in cortisol have been found to lengthen wound healing time in healthy, male adults. Those who had the lowest levels of cortisol the day following a 4 mm punch biopsy had the fastest healing time.[37] In dental students, wounds from punch biopsies took an average of 40% longer to heal when performed three days before an examination as opposed to biopsies performed on the same students during summer vacation.[38]

In mice, glucocorticoids have been shown to increase following an acute stressor. Wounded mice that underwent a restrained stress test took an average of 3.10 days longer to heal than control mice. In addition, glucocorticoids were shown to increase in the restraint stress test mice, but not in control mice or restraint test mice given a glucocorticoid receptor antagonist.[39] In a study of Siberian hamsters, stress only increased glucocorticoids and wound healing time in rodents that were exposed to a stressor and kept in isolation. Social facilitation speeded wound healing time, mitigating the effects of the stressor.[40]


Cortisol counteracts insulin, contributes to hyperglycemia-causing hepatic gluconeogenesis[41] and inhibits the peripheral utilization of glucose (insulin resistance)[41] by decreasing the translocation of glucose transporters (especially GLUT4) to the cell membrane.[42][43] However, cortisol increases glycogen synthesis (glycogenesis) in the liver.[44] 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.

Amino acids[edit]

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.[45] Cortisol (as opticortinol) may inversely inhibit IgA precursor cells in the intestines of calves.[46] Cortisol also inhibits IgA in serum, as it does IgM; however, it is not shown to inhibit IgE.[47]

Gastric and renal secretion[edit]

Cortisol stimulates gastric-acid secretion.[48] 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.[49] Net chloride secretion in the intestines is inversely decreased by cortisol in vitro (methylprednisolone).[50]

Electrolyte and water balance[edit]

Cortisol acts as a diuretic, increasing water diuresis, glomerular filtration rate, and renal plasma flow from the kidneys, as well as increasing sodium retention and potassium excretion. It also increases sodium and water absorption and potassium excretion in the intestines.[51]


Cortisol stimulates many copper enzymes (often to 50% of their total potential), probably to increase copper availability for immune purposes.[52]:337 This includes lysyl oxidase, an enzyme that cross-links collagen and elastin.[52]:334 Especially valuable for immune response is cortisol's stimulation of the superoxide dismutase,[53] 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;[54] 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.[55] If alpha-aminoisobuteric acid is used to transport copper through the cell wall, this anomaly might be explained.


Cortisol inhibits sodium loss through the small intestine of mammals.[56] Sodium depletion, however, does not affect cortisol levels[57] 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.[58]


A sodium load augments the intense potassium excretion by cortisol. Corticosterone is comparable to cortisol in this case.[44] For potassium to move out of the cell, cortisol moves an equal number of sodium ions into the cell.[33] 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).[59]


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.[60] However, long-term exposure to cortisol damages cells in the hippocampus;[61] this damage results in impaired learning. Furthermore, it has been shown that cortisol inhibits memory retrieval of already stored information.[62][63]

Additional effects[edit]

  • A 2010 study found that serum cortisol predicts increased cardiovascular mortality in patients with acute coronary syndrome.[64][65]
  • Increases blood pressure by increasing the sensitivity of the vasculature to epinephrine and norepinephrine; in the absence of cortisol, widespread vasodilation occurs[60]
  • Inhibits secretion of corticotropin-releasing hormone (CRH), resulting in feedback inhibition of ACTH (Adrenocorticotropic hormone or corticotropin) secretion. Some researchers believe that this normal feedback system may become dysregulated when animals are exposed to chronic stress[66]
  • Causes the kidneys to produce hypotonic urine[60]
  • 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.[67]
  • Has anti-inflammatory properties, reducing histamine secretion and stabilizing lysosomal membranes. Stabilization of lysosomal membranes prevents their rupture, preventing damage to healthy tissues[68]
  • Stimulates hepatic detoxification by inducing tryptophan oxygenase (reducing serotonin levels in the brain), glutamine synthase (reducing glutamate and ammonia levels in the brain), cytochrome P-450 hemoprotein (mobilizing arachidonic acid), and metallothionein (reducing heavy metals in the body)[69]
  • 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[69]
  • There are potential links between cortisol, appetite, and obesity.[70]


Diurnal cycles of cortisol levels are found in several animal species, including humans.[6] In species that exhibit such cycles, different timing of diurnal maxima and minima has been observed, not only in different species[6] but also, in some cases, within the same species.[71][72][73]

In humans, the amount of cortisol present in the blood undergoes diurnal variation; the level peaks in the early morning (approximately 8 a.m.) and reaches its lowest level at about midnight-4 a.m., 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.[74]

Changed patterns of serum cortisol levels have been observed in connection with abnormal ACTH levels, clinical depression, psychological stress, and physiological stressors such as hypoglycemia, illness, fever, trauma, surgery, fear, pain, physical exertion, or temperature extremes. Cortisol levels may also differ for individuals with autism or Asperger's syndrome.[75]

There is also significant individual variation, although a given person tends to have consistent rhythms.[76]

Ultradian as well as circadian cycles of cortisol secretion have been observed, e.g. a cycle period of about 2 h in cattle[77] and about 1 h in sheep.[71]


Most serum cortisol (all but about 4%) is bound to proteins, including corticosteroid binding globulin (CBG) and serum albumin. Free cortisol passes easily through cellular membranes, where they bind intracellular cortisol receptors.[78]


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.[79] 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.[80] (In swine, which do not produce arginine vasopressin, lysine vasopressin acts synergistically with CRH.[81])

When activated macrophages start to secrete interleukin-1 (IL-1), which synergistically with CRH increases ACTH,[30] 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.[31] 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.[82] 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[30]—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,[31] 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.[83]

High-potassium media (which stimulates aldosterone secretion in vitro) also stimulate cortisol secretion from the fasciculata zone of canine adrenals [84][85] — unlike corticosterone, upon which potassium has no effect.[86]

Potassium loading also increases ACTH and cortisol in humans.[87] 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.[88] This may also have a role in rheumatoid-arthritis pain; cell potassium is always low in RA.[89]

Factors generally reducing cortisol levels[edit]

  • Magnesium supplementation decreases serum cortisol levels after aerobic exercise,[90][91] but not after resistance training.[92]
  • Omega-3 fatty acids have a dose-dependent effect[93] in slightly reducing cortisol release influenced by mental stress,[94] 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.[95]
  • Music therapy can reduce cortisol levels in certain situations.[96]
  • Massage therapy can reduce cortisol.[97]
  • Laughing, and the experience of humour, can lower cortisol levels.[98]
  • Soy-derived phosphatidylserine interacts with cortisol; the correct dose, however, is unclear.[99][100]
  • Black tea may hasten recovery from a high-cortisol condition.[101][102][103]
  • Regular dancing has been shown to lead to significant decreases in salivary cortisol concentrations.[104]

Factors generally increasing cortisol levels[edit]

  • Viral infections increase cortisol levels through activation of the HPA axis by cytokines.[105]
  • Caffeine may increase cortisol levels.[106]
  • Sleep deprivation[107]
  • Intense (high VO2 max) or prolonged physical exercise stimulates cortisol release to increase gluconeogenesis and maintain blood glucose.[108] Proper nutrition[109] and high-level conditioning[110] 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.[111]
  • Hypoestrogenism and melatonin supplementation increase cortisol levels in postmenopausal women.[112]
  • Severe trauma or stressful events can elevate cortisol levels in the blood for prolonged periods.[113][114]
  • Subcutaneous adipose tissue regenerates cortisol from cortisone.[115]
  • Anorexia nervosa may be associated with increased cortisol levels.[116]
  • The serotonin receptor gene 5HTR2C is associated with increased cortisol production in men.[117]
  • Stimuli associated with sexual intercourse can increase cortisol levels in gilts (a young female pig that has not produced her first litter).[118]
  • Severe calorie restriction causes elevated baseline levels of cortisol.[119]
  • Continuous consumption of alcohol over an extended period of time has been shown to raise cortisol levels in the body.
  • Posing in low-power nonverbal displays through close, contractive postures can increase cortisol levels.[120]
  • Smelling androstadienone has been found in one study to raise cortisol levels in women; as well as, in other studies, to affect mood (see androstadienone article for details and citations).


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.

Compared to hydrocortisone, prednisolone is about four times as strong and dexamethasone about forty times as strong, in their anti-inflammatory effect.[121] For side effects, see corticosteroid and prednisolone.

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.[122]



Steroidogenesis, showing cortisol at right.

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[123] or exceed.[6] cortisol levels.). The medulla of the adrenal gland lies under the cortex, mainly secreting the catecholamines adrenaline (epinephrine) and noradrenaline (norepinephrine) under sympathetic stimulation.

The synthesis of cortisol in the adrenal gland is stimulated by the anterior lobe of the pituitary gland with adrenocorticotropic hormone (ACTH); ACTH production is in turn stimulated by corticotropin-releasing hormone (CRH), which is released by the hypothalamus. ACTH increases the concentration of cholesterol in the inner mitochondrial membrane, via regulation of the STAR (steroidogenic acute regulatory) protein. It also stimulates the main rate-limiting step in cortisol synthesis, in which cholesterol is converted to pregnenolone and catalyzed by Cytochrome P450SCC (side-chain cleavage enzyme).[124]


Cortisol is metabolized by the 11-beta hydroxysteroid dehydrogenase system (11-beta HSD), which consists of two enzymes: 11-beta HSD1 and 11-beta HSD2.

  • 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).

An alteration in 11-beta HSD1 has been suggested to play a role in the pathogenesis of obesity, hypertension, and insulin resistance known as metabolic syndrome.[125]

An alteration in 11-beta HSD2 has been implicated in essential hypertension and is known to lead to the syndrome of apparent mineralocorticoid excess (SAME).

Health disparities[edit]

By measuring salivary cortisol, researchers have found a decrease in cortisol concentration in people with leadership roles as compared to non-leadership roles. The results were independent of differences in education and income.[126]

Cortisol, as well as other glucocorticoids, have been used as biomarkers of psychological stress.[127]

Lower socioeconomic status is associated with higher evening levels of cortisol.[128]

Obese patients have higher hair cortisol levels than overweight and normal weight subjects.[129]


For the synthesis steps, see on the cortisone page.

See also[edit]


  1. ^ a b Scott E (2011-09-22). "Cortisol and Stress: How to Stay Healthy". Retrieved 2011-11-29. [better source needed]
  2. ^ Hoehn K, Marieb EN (2010). Human Anatomy & Physiology. San Francisco: Benjamin Cummings. ISBN 0-321-60261-7. 
  3. ^ a b Chyun Y, Kream B, Raisz L (1984). "Cortisol decreases bone formation by inhibiting periosteal cell proliferation". Endocrinology 114 (2): 477–80. doi:10.1210/endo-114-2-477. PMID 6690287. 
  4. ^ "WHO Model List of EssentialMedicines". World Health Organization. October 2013. Retrieved 22 April 2014. 
  5. ^ | "Hormones-cortisol". Home Better Health Channel. 2014 State Government of Victoria. June 2013. Retrieved 2014-04-01. 
  6. ^ a b c d Martin PA, Crump MH (2003). "The adrenal gland". In Dooley MP, Pineda MH. McDonald's veterinary endocrinology and reproduction (5th ed.). Ames, Iowa: Iowa State Press. ISBN 0-8138-1106-6. 
  7. ^ Coderre L, Srivastava A, Chiasson J (June 1991). "Role of glucocorticoid in the regulation of glycogen metabolism in skeletal muscle". Am. J. Physiol. 260 (6 Pt 1): E927–32. PMID 1905485. 
  8. ^ Simmons P, Miles J, Gerich J, Haymond M (February 1984). "Increased proteolysis. An effect of increases in plasma cortisol within the physiologic range". J. Clin. Invest. 73 (2): 412–20. doi:10.1172/JCI111227. PMC 425032. PMID 6365973. 
  9. ^ Djurhuus C, Gravholt C, Nielsen S, Mengel A, Christiansen J, Schmitz O et al. (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 (inactive 2015-01-11). PMID 12067858. 
  10. ^ Elenkov I (2004). "Glucocorticoids and the Th1/Th2 Balance". Annals of the New York Academy of Sciences 1024 (1): 138–146. Bibcode:2004NYASA1024..138E. doi:10.1196/annals.1321.010. PMID 15265778. 
  11. ^ "You & Your Hormones : Cortisol". the Society for Endocrinology (Last updated) :. October 24, 2013. Archived from the original on November 24, 2014. Retrieved November 24, 2014. 
  12. ^ a b c d Biochemistry Reference Ranges at Good Hope Hospital Retrieved 8 November 2009[better source needed]
  13. ^ a b c d Derived from molar values using molar mass of 362 g/mol
  14. ^ a b Converted from µg/24h, using molar mass of 362.460 g/mol
  15. ^ a b Görges R, 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". J. Endocrinol. Invest. 22 (4): 241–9. doi:10.1007/bf03343551. PMID 10342356. 
  16. ^ a b MedlinePlus Encyclopedia Cortisol – urine
  17. ^ a b Converted from nmol/24h, using molar mass of 362.460 g/mol
  18. ^ Mescher E, Platzker A, Ballard P, Kitterman J, Clements J, Tooley W (December 1975). "Ontogeny of tracheal fluid, pulmonary surfactant, and plasma corticoids in the fetal lamb". J Appl Physiol 39 (6): 1017–21. PMID 2573. 
  19. ^ Hennessy D, Coghlan J, Hardy K, Scoggins B, Wintour E (October 1982). "The origin of cortisol in the blood of fetal sheep". J. Endocrinol. 95 (1): 71–9. doi:10.1677/joe.0.0950071. PMID 7130892. 
  20. ^ Magyar D, Fridshal D, Elsner C, Glatz T, Eliot J, Klein A et al. (July 1980). "Time-trend analysis of plasma cortisol concentrations in the fetal sheep in relation to parturition". Endocrinology 107 (1): 155–9. doi:10.1210/endo-107-1-155. PMID 7379742. 
  21. ^ Ricketts A, Flint A (August 1980). "Onset of synthesis of progesterone by ovine placenta". J. Endocrinol. 86 (2): 337–47. doi:10.1677/joe.0.0860337. PMID 6933207. 
  22. ^ Al-Gubory K, 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. PMID 10972299. 
  23. ^ 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. ISBN 0-683-30577-8. 
  24. ^ Mustoe A, Birnie A, Korgan A, Santo J, French J (February 2012). "Natural variation in gestational cortisol is associated with patterns of growth in marmoset monkeys (Callithrix geoffroyi)". Gen. Comp. Endocrinol. 175 (3): 519–26. doi:10.1016/j.ygcen.2011.12.020. PMC 3268124. PMID 22212825. 
  25. ^ Feng X, Wang L, Yang S, Qin D, Wang J, Li C et al. (2011). "Maternal separation produces lasting changes in cortisol and behavior in rhesus monkeys". Proc. Natl. Acad. Sci. U.S.A. 108 (34): 14312–7. Bibcode:2011PNAS..10814312F. doi:10.1073/pnas.1010943108. PMC 3161556. PMID 21844333. 
  26. ^ a b Kumari M, Head J, Bartley M, Stansfeld S, Kivimaki M (July 2012). "Maternal separation in childhood and diurnal cortisol patterns in mid-life: findings from the Whitehall II study". Psychological Medicine 43 (3): 633–643. doi:10.1017/S0033291712001353. PMID 22785027. 
  27. ^ Pesonen A, Räikkönen K, Feldt K, Heinonen K, Osmond C, Phillips D et al. (April 2010). "Childhood separation experience predicts HPA axis hormonal responses in late adulthood: A natural experience of World War II". Psychoneuroendocrinology 35 (5): 785–767. doi:10.1016/j.psyneuen.2009.10.017. PMID 19963324. 
  28. ^ Diamond L, Hicks A, Otter-Henderson K (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 Psychology 95 (2): 385–493. doi:10.1037/0022-3514.95.2.385. PMID 18665709. 
  29. ^ 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 Immunology 15 (1): 25–31. doi:10.1111/j.1365-3083.1982.tb00618.x. PMID 6461917. 
  30. ^ a b c Besedovsky 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. 
  31. ^ a b c Fairchild S, Shannon K, Kwan E, Mishell R (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 Immunology 132 (2): 821–7. PMID 6228602. 
  32. ^ Mavoungou E, Bouyou-Akotet M, Kremsner P (2005). "Effects of prolactin and cortisol on natural killer (NK) cell surface expression and function of human natural cytotoxicity receptors (NKp46, NKp44 and NKp30)". Clin. Exp. Immunol. 139 (2): 287–96. doi:10.1111/j.1365-2249.2004.02686.x. PMC 1809301. PMID 15654827. 
  33. ^ a b Knight R, Kornfeld D, Glaser G, Bondy P (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. PMID 13233328. 
  34. ^ Deutsch E (April 1978). "[Pathogenesis of thrombocytopenia. 2. Distribution disorders, pseudo-thrombocytopenias]". Fortschr. Med. (in German) 96 (14): 761–2. PMID 346457. 
  35. ^ Kucharz E (1988). "Hormonal control of collagen metabolism. Part II". Endocrinologie 26 (4): 229–37. PMID 3062759. 
  36. ^ Houck J, Sharma V, Patel Y, Gladner J (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. PMID 4301453. 
  37. ^ Ebrecht M, Hextall J, Kirtley L, Taylor A, Dyson M, Weinman J (2004). "Perceived stress and cortisol levels predict speed of wound healing in healthy male adults". Psychoneuroendocrinology 29 (6): 798–809. doi:10.1016/s0306-4530(03)00144-6. PMID 15110929. 
  38. ^ Marucha P, Kiecolt-Glaser J, Favagehi M (1998). "Mucosal wound healing is impaired by examination stress". Psychosom Med 60 (3): 362–5. doi:10.1097/00006842-199805000-00025. PMID 9625226. 
  39. ^ Padgett D, Marucha P, Sheridan J (1998). "Restraint stress slows cutaneous wound healing in mice". Brain Behav. Immun. 12 (1): 64–73. doi:10.1006/brbi.1997.0512. PMID 9570862. 
  40. ^ Detillion C, Craft T, Glasper E, Prendergast B, DeVries A (2004). "Social facilitation of wound healing". Psychoneuroendocrinology 29 (8): 1004–11. doi:10.1016/j.psyneuen.2003.10.003. PMID 15219651. 
  41. ^ a b Brown DF, Brown DD (2003). USMLE Step 1 Secrets: Questions You Will Be Asked on USMLE Step 1. Philadelphia: Hanley & Belfus. p. 63. ISBN 1-56053-570-9. [better source needed]
  42. ^ King MB (2005). Lange Q & A. New York: McGraw-Hill, Medical Pub. Division. ISBN 0-07-144578-1. 
  43. ^ Piroli G, Grillo C, Reznikov L, Adams S, McEwen B, Charron M et al. (2007). "Corticosterone impairs insulin-stimulated translocation of GLUT4 in the rat hippocampus". Neuroendocrinology 85 (2): 71–80. doi:10.1159/000101694. PMID 17426391. 
  44. ^ a b Baynes J, Dominiczak M (2009). Medical biochemistry. Mosby Elsevier. ISBN 0-323-05371-8. 
  45. ^ 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?. 
  46. ^ Husband A, Brandon M, Lascelles A (October 1973). "The effect of corticosteroid on absorption and endogenous production of immunoglobulins in calves". Aust J Exp Biol Med Sci 51 (5): 707–10. doi:10.1038/icb.1973.67. PMID 4207041. 
  47. ^ Posey W, Nelson H, Branch B, Pearlman D (December 1978). "The effects of acute corticosteroid therapy for asthma on serum immunoglobulin levels". The Journal of Allergy and Clinical Immunology 62 (6): 340–8. doi:10.1016/0091-6749(78)90134-3. PMID 712020. 
  48. ^ Soffer LJ, Dorfman RI, Gabrilove JL (1961). The Human Adrenal Gland. Philadelphia: Lea & Febiger. 
  49. ^ Posey W, Nelson H, Branch B, Pearlman D (December 1979). "Role of Glucocorticoids in Regulation of the Acid-Excreting Function of the Kidneys". Fiziol. Z H SSR I.M.I.M. Sechenova 65 (6): 340–8. doi:10.1016/0091-6749(78)90134-3. PMID 712020. 
  50. ^ Tai Y, Decker R, Marnane W, Charney A, Donowitz M (May 1981). "Effects of methylprednisolone on electrolyte transport by in vitro rat ileum". Am. J. Physiol. 240 (5): G365–70. PMID 6112881. 
  51. ^ Physiologic and Pharmacologic Effects of Corticosteroids. 2003. 
  52. ^ a b Weber C (December 1984). "Copper response to rheumatoid arthritis". Med. Hypotheses 15 (4): 333–48. doi:10.1016/0306-9877(84)90150-6. PMID 6152006. 
  53. ^ Flohe L, Beckman R, Giertz H, Loschen G (1985). "Oxygen Centered Free Radicals as Mediators of Inflammation". In Sies H. Oxidative stress. London: Orlando. p. 405. ISBN 0-12-642760-7. 
  54. ^ Piletz J, Herschman H (June 1983). "Hepatic metallothionein synthesis in neonatal Mottled-Brindled mutant mice". Biochem. Genet. 21 (5–6): 465–75. doi:10.1007/BF00484439. PMID 6870774. 
  55. ^ Chambers J, Georg R, Bass A (July 1965). "Effect of hydrocortisone and insulin on uptake of alpha-aminoisobutyric acid by isolated perfused rat liver". Mol. Pharmacol. 1 (1): 66–76. PMID 5835080. 
  56. ^ Sandle G, Keir M, Record C (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. PMID 7323700. 
  57. ^ Mason P, Fraser R, Morton J, Semple P, 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. PMID 592808. 
  58. ^ Gorbman A, Dickhoff WW, Vigna SR, Clark NB, Muller AF (1983). Comparative endocrinology. New York: Wiley. ISBN 0-471-06266-9. 
  59. ^ Barger A, Berlin R, Tulenko J (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". Endocrinology 62 (6): 804–15. doi:10.1210/endo-62-6-804. PMID 13548099. 
  60. ^ a b c Kennedy, Ron. "Cortisol (Hydrocortisone)". The Doctors' Medical Library. Retrieved 14 June 2013. 
  61. ^ McAuley M, Kenny R, Kirkwood T, Wilkinson D, Jones J, Miller V (2009). "A mathematical model of aging-related and cortisol induced hippocampal dysfunction". BMC Neurosci 10: 26. doi:10.1186/1471-2202-10-26. PMC 2680862. PMID 19320982. 
  62. ^ de Quervain D, Roozendaal B, McGaugh J (August 1998). "Stress and glucocorticoids impair retrieval of long-term spatial memory". Nature 394 (6695): 787–90. Bibcode:1998Natur.394..787D. doi:10.1038/29542. PMID 9723618. 
  63. ^ de Quervain D, Roozendaal B, Nitsch R, McGaugh J, Hock C (April 2000). "Acute cortisone administration impairs retrieval of long-term declarative memory in humans". Nat. Neurosci. 3 (4): 313–4. doi:10.1038/73873. PMID 10725918. 
  64. ^ "Serum cortisol predicts increased cardiovascular mortality in patients with acute coronary syndrome". Retrieved 2010-06-14. 
  65. ^ Terzolo M, Bovio S, Pia A, Conton P, Reimondo G, Dall'Asta C et al. (2005). "Midnight serum cortisol as a marker of increased cardiovascular risk in patients with a clinically inapparent adrenal adenoma". Eur. J. Endocrinol. 153 (2): 307–15. doi:10.1530/eje.1.01959. PMID 16061838. 
  66. ^ Holsboer, Florian. "Holsboer". Retrieved 14 June 2013. 
  67. ^ Nelson RF (2011). An Introduction to Behavioral Endocrinology, Fourth Edition. Sunderland, Mass: Sinauer Associates Inc. ISBN 0-87893-620-3. 
  68. ^ Anosike C, Obidoa O, Ezeanyika L (2012). "US National Library of Medicine National Institutes of Health". DARU Journal of Pharmaceutical Sciences (US National Library of Medicine National Institutes of Health) 20 (1): 76. doi:10.1186/2008-2231-20-76. PMC 3556049. PMID 23351977. 
  69. ^ a b "Cortisol & the Counter-Regulatory Hormones". Retrieved 14 June 2013. 
  70. ^ Maglione-Garves CA, Kravitz L, Schneider S. "Stress Cortisol Connection: Tips on Managing Stress and Weight". University of New Mexico. Retrieved 2010-06-14. 
  71. ^ a b Fulkerson W, Tang B (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. PMID 469453. 
  72. ^ 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. PMID 6889565. 
  73. ^ Simonetta G, Walker D, McMillen I (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. PMID 1647800. 
  74. ^ de Weerth C, Zijl R, Buitelaar J (August 2003). "Development of cortisol circadian rhythm in infancy". Early Hum. Dev. 73 (1–2): 39–52. doi:10.1016/S0378-3782(03)00074-4. PMID 12932892. 
  75. ^ "Asperger's stress hormone 'link'". BBC News Online. 2009-04-02. Retrieved 2010-04-30. 
  76. ^ "The Canary Club". The Canary Club. Retrieved 3 July 2013. 
  77. ^ Lefcourt A, Bitman J, Kahl S, Wood D (September 1993). "Circadian and ultradian rhythms of peripheral cortisol concentrations in lactating dairy cows". J. Dairy Sci. 76 (9): 2607–12. doi:10.3168/jds.S0022-0302(93)77595-5. PMID 8227661. 
  78. ^ Boron WF, Boulpaep EL (2011). Medical Physiology (2nd ed.). Philadelphia: Saunders. ISBN 1-4377-1753-5. 
  79. ^ Davies E, Kenyon C, Fraser R (1985). "The role of calcium ions in the mechanism of ACTH stimulation of cortisol synthesis". Steroids 45 (6): 551–60. doi:10.1016/0039-128X(85)90019-4. PMID 3012830. 
  80. ^ Plotsky P, Otto S, Sapolsky R (September 1986). "Inhibition of immunoreactive corticotropin-releasing factor secretion into the hypophysial-portal circulation by delayed glucocorticoid feedback". Endocrinology 119 (3): 1126–30. doi:10.1210/endo-119-3-1126. PMID 3015567. 
  81. ^ Minton J, Parsons K (March 1993). "Adrenocorticotropic hormone and cortisol response to corticotropin-releasing factor and lysine vasopressin in pigs". J. Anim. Sci. 71 (3): 724–9. PMID 8385088. 
  82. ^ Dvorak M (1971). "Plasma 17-Hydroxycorticosteroid Levels in Healthy and Diarrheic Calves". British Veterinarian Journal 127: 372. 
  83. ^ Stith R, McCallum R (1986). "General effect of endotoxin on glucocorticoid receptors in mammalian tissues". Circ. Shock 18 (4): 301–9. PMID 3084123. 
  84. ^ Mikosha A, Pushkarov I, Chelnakova I, Remennikov G (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. 
  85. ^ "Ameer Saadallah Al – Zacko". Retrieved 11 July 2013. 
  86. ^ Mendelsohn F, Mackie C (July 1975). "Relation of intracellular K+ and steroidogenesis in isolated adrenal zona glomerulosa and fasciculata cells". Clin Sci Mol Med 49 (1): 13–26. PMID 168026. 
  87. ^ Ueda Y, Honda M, Tsuchiya M, Watanabe H, Izumi Y, Shiratsuchi T et al. (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. PMID 6283190. 
  88. ^ 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. 
  89. ^ LaCelle P 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 Rheumatism 7: 321. 
  90. ^ Golf S, Happel O, Graef V, Seim K (1984). "Plasma aldosterone, cortisol and electrolyte concentrations in physical exercise after magnesium supplementation". J. Clin. Chem. Clin. Biochem. 22 (11): 717–21. doi:10.1515/cclm.1984.22.11.717. PMID 6527092. 
  91. ^ Golf S, Bender S, Grüttner J (1998). "On the significance of magnesium in extreme physical stress". Cardiovasc Drugs Ther. 12 Suppl 2 (2suppl): 197–202. doi:10.1023/A:1007708918683. PMID 9794094. 
  92. ^ Wilborn C, Kerksick C, Campbell B, Taylor L, Marcello B, Rasmussen C et al. (2004). "Effects of Zinc Magnesium Aspartate (ZMA) Supplementation on Training Adaptations and Markers of Anabolism and Catabolism". J Int Soc Sports Nutr 1 (2): 12–20. doi:10.1186/1550-2783-1-2-12. PMC 2129161. PMID 18500945. 
  93. ^ Bhathena S, Berlin E, Judd J, Kim Y, Law J, Bhagavan H et al. (1991). "Effects of omega 3 fatty acids and vitamin E on hormones involved in carbohydrate and lipid metabolism in men". Am. J. Clin. Nutr. 54 (4): 684–8. PMID 1832814. 
  94. ^ Delarue J, Matzinger O, Binnert C, Schneiter P, Chioléro R, Tappy L (2003). "Fish oil prevents the adrenal activation elicited by mental stress in healthy men". Diabetes Metab. 29 (3): 289–95. doi:10.1016/S1262-3636(07)70039-3. PMID 12909818. 
  95. ^ Yehuda S (2003). "Omega-6/omega-3 ratio brain related functions". In Simopoulos AP, Cleland LG. Omega-6, omega-3 essential fatty acid ratio: the scientific evidence. Basel: Karger. p. 50. ISBN 3-8055-7640-4. 
  96. ^ Uedo N, Ishikawa H, Morimoto K, Ishihara R, Narahara H, Akedo I et al. (2004). "Reduction in salivary cortisol level by music therapy during colonoscopic examination". Hepatogastroenterology 51 (56): 451–3. PMID 15086180. 
  97. ^ Field T, Hernandez-Reif M, Diego M, Schanberg S, Kuhn C (2005). "Cortisol decreases and serotonin and dopamine increase following massage therapy". Int. J. Neurosci. 115 (10): 1397–413. doi:10.1080/00207450590956459. PMID 16162447. 
  98. ^ Berk LS, Tan SA, Berk D (2008). "Cortisol and Catecholamine stress hormone decrease is associated with the behavior of perceptual anticipation of mirthful laughter". The FASEB Journal 22 (1): 946.11. 
  99. ^ Hellhammer J, Fries E, Buss C, Engert V, Tuch A, Rutenberg D et al. (2004). "Effects of soy lecithin phosphatidic acid and phosphatidylserine complex (PAS) on the endocrine and psychological responses to mental stress". Stress 7 (2): 119–26. doi:10.1080/10253890410001728379. PMID 15512856. 
  100. ^ Starks M, Starks S, Kingsley M, Purpura M, Jäger R (2008). "The effects of phosphatidylserine on endocrine response to moderate intensity exercise". J Int Soc Sports Nutr 5: 11. doi:10.1186/1550-2783-5-11. PMC 2503954. PMID 18662395. 
  101. ^ "Black tea 'soothes away stress'". BBC News Online. 2006-10-04. Retrieved 2010-04-30. 
  102. ^ Steptoe A, Gibson E, Vuononvirta R, Williams E, Hamer M, Rycroft J et al. (2007). "The effects of tea on psychophysiological stress responsivity and post-stress recovery: a randomised double-blind trial". Psychopharmacology (Berl.) 190 (1): 81–9. doi:10.1007/s00213-006-0573-2. PMID 17013636. 
  103. ^ "medicalnewstoday". Retrieved 25 September 2013. 
  104. ^ Quiroga M, Bongard S, Kreutz G (July 2009). "Emotional and Neurohumoral Responses to Dancing Tango Argentino: The Effects of Music and Partner". Music and Medicine 1 (1): 14–21. doi:10.1177/1943862109335064. 
  105. ^ Silverman M, Pearce B, Biron C, Miller A (2005). "Immune Modulation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis during Viral Infection". Viral Immunology 18 (1): 41–78. doi:10.1089/vim.2005.18.41. PMC 1224723. PMID 15802953. 
  106. ^ Lovallo W, Farag N, Vincent A, Thomas T, Wilson M (March 2006). "Cortisol responses to mental stress, exercise, and meals following caffeine intake in men and women". Pharmacol. Biochem. Behav. 83 (3): 441–7. doi:10.1016/j.pbb.2006.03.005. PMC 2249754. PMID 16631247. 
  107. ^ Leproult R, Copinschi G, Buxton O, Van Cauter E (October 1997). "Sleep loss results in an elevation of cortisol levels the next evening". Sleep 20 (10): 865–70. PMID 9415946. 
  108. ^ Robson P, Blannin A, Walsh N, Castell L, Gleeson M (February 1999). "Effects of exercise intensity, duration and recovery on in vitro neutrophil function in male athletes". Int J Sports Med 20 (2): 128–35. doi:10.1055/s-2007-971106. PMID 10190775. 
  109. ^ Gleeson M (2006). "Can nutrition limit exercise-induced immunodepression?". Nutr. Rev. 64 (3): 119–31. doi:10.1111/j.1753-4887.2006.tb00195.x. PMID 16572599. 
  110. ^ Kraemer W, Spiering B, Volek J, Martin G, Howard R, Ratamess N et al. (January 2009). "Recovery from a national collegiate athletic association division I football game: muscle damage and hormonal status". J Strength Cond Res 23 (1): 2–10. doi:10.1519/JSC.0b013e31819306f2. PMID 19077734. 
  111. ^ Shalev I, Lerer E, Israel S, Uzefovsky F, Gritsenko I, Mankuta D et al. (2009). "BDNF Val66Met polymorphism is associated with HPA axis reactivity to psychological stress characterized by genotype and gender interactions". Psychoneuroendocrinology 34 (3): 382–8. doi:10.1016/j.psyneuen.2008.09.017. PMID 18990498. 
  112. ^ Cagnacci A, Soldani R, Yen S (1997). "Melatonin enhances cortisol levels in aged women: reversible by estrogens". J. Pineal Res. 22 (2): 81–5. doi:10.1111/j.1600-079X.1997.tb00307.x. PMID 9181519. 
  113. ^ Smith JL, Gropper SAS, Groff JL (2009). Advanced nutrition and humanmetabolism. Belmont, CA: Wadsworth Cengage Learning. p. 247. ISBN 0-495-11657-2. 
  114. ^ Moberg GP, Mench JA (2000). The biology of animal stress: basic principles and implications for animal welfare. Wallingford, Oxon, UK: CABI Pub. p. 377. ISBN 0-85199-359-1. 
  115. ^ Stimson R, Andersson J, Andrew R, Redhead D, Karpe F, Hayes P et al. (January 2009). "Cortisol release from adipose tissue by 11beta-hydroxysteroid dehydrogenase type 1 in humans". Diabetes 58 (1): 46–53. doi:10.2337/db08-0969. PMC 2606892. PMID 18852329. 
  116. ^ Haas V, Kohn M, Clarke S, Allen J, Madden S, Müller M et al. (April 2009). "Body composition changes in female adolescents with anorexia nervosa". Am. J. Clin. Nutr. 89 (4): 1005–10. doi:10.3945/ajcn.2008.26958. PMID 19211813. 
  117. ^ Brummett B, Kuhn C, Boyle S, Babyak M, Siegler I, Williams R (January 2012). "Cortisol responses to emotional stress in men: association with a functional polymorphism in the 5HTR2C gene". Biol Psychol 89 (1): 94–8. doi:10.1016/j.biopsycho.2011.09.013. PMC 3245751. PMID 21967853. 
  118. ^ 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 Biol 2 (1): 25–37. PMID 14666160. 
  119. ^ Fichter M, Pirke K, Holsboer F (January 1986). "Weight loss causes neuroendocrine disturbances: experimental study in healthy starving subjects". Psychiatry Res 17 (1): 61–72. doi:10.1016/0165-1781(86)90042-9. PMID 3080766. 
  120. ^ Carney D, Cuddy A, Yap A (September 2010). "Power posing: brief nonverbal displays affect neuroendocrine levels and risk tolerance". Psychol Sci. 21 (10): 1363–1368. doi:10.1177/0956797610383437. PMID 20855902. 
  121. ^ "Dexamethasone". Retrieved 14 June 2013. 
  122. ^ Iwata, Edward (5 January 2007). "Diet pill sellers fined $25M". USA Today. Retrieved 2008-10-26. 
  123. ^ Willett L, Erb R (January 1972). "Short term changes in plasma corticoids in dairy cattle". J. Anim. Sci. 34 (1): 103–11. PMID 5062063. 
  124. ^ Margioris AN, Tsatsanis C (2011). "ACTH Action on the Adrenal". In Chrousos G. Adrenal physiology and diseases. 
  125. ^ Tomlinson J, Walker E, Bujalska I, Draper N, Lavery G, Cooper M et al. (October 2004). "11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response". Endocr. Rev. 25 (5): 831–66. doi:10.1210/er.2003-0031. PMID 15466942. 
  126. ^ Sherman G, Lee J, Cuddy A, Renshon J, Oveis C, Gross J et al. (October 2012). "Leadership is associated with lower levels of stress". Proc. Natl. Acad. Sci. U.S.A. 109 (44): 17903–7. Bibcode:2012PNAS..10917903S. doi:10.1073/pnas.1207042109. PMC 3497788. PMID 23012416. 
  127. ^ Djuric Z, Bird C, Furumoto-Dawson A, Rauscher G, Ruffin M, Stowe R et al. (2008). "Biomarkers of Psychological Stress in Health Disparities Research". Open Biomark J 1: 7–19. doi:10.2174/1875318300801010007. PMC 2841407. PMID 20305736. 
  128. ^ Cohen S, Schwartz J, 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". Psychosom Med 68 (1): 41–50. doi:10.1097/01.psy.0000195967.51768.ea. PMID 16449410. 
  129. ^ Wester V, Staufenbiel S, Veldhorst M, Visser J, Manenschijn L, Koper J et al. (2014). "Long-term cortisol levels measured in scalp hair of obese patients". Obesity (Silver Spring) 22 (9): 1956–8. doi:10.1002/oby.20795. PMID 24852462.  [Epub ahead of print]

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