Cortisol
Overview
Cortisol is a steroid
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...

 hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...

, more specifically a glucocorticoid
Glucocorticoid
Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell...

, produced by the adrenal gland
Adrenal gland
In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...

. It is released in response to stress
Stress (medicine)
Stress is a term in psychology and biology, borrowed from physics and engineering and first used in the biological context in the 1930s, which has in more recent decades become commonly used in popular parlance...

 and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar
Blood sugar
The blood sugar concentration or blood glucose level is the amount of glucose present in the blood of a human or animal. Normally in mammals, the body maintains the blood glucose level at a reference range between about 3.6 and 5.8 mM , or 64.8 and 104.4 mg/dL...

 through gluconeogenesis
Gluconeogenesis
Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids....

; suppress the immune system; and aid in fat, protein and carbohydrate metabolism. It also decreases bone formation. During pregnancy, increased production of cortisol between weeks 30-32 initiates production of fetal lung surfactant to promote maturation of the lungs.
Encyclopedia
Cortisol is a steroid
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...

 hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...

, more specifically a glucocorticoid
Glucocorticoid
Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell...

, produced by the adrenal gland
Adrenal gland
In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...

. It is released in response to stress
Stress (medicine)
Stress is a term in psychology and biology, borrowed from physics and engineering and first used in the biological context in the 1930s, which has in more recent decades become commonly used in popular parlance...

 and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar
Blood sugar
The blood sugar concentration or blood glucose level is the amount of glucose present in the blood of a human or animal. Normally in mammals, the body maintains the blood glucose level at a reference range between about 3.6 and 5.8 mM , or 64.8 and 104.4 mg/dL...

 through gluconeogenesis
Gluconeogenesis
Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids....

; suppress the immune system; and aid in fat, protein and carbohydrate metabolism. It also decreases bone formation. During pregnancy, increased production of cortisol between weeks 30-32 initiates production of fetal lung surfactant to promote maturation of the lungs. Various synthetic forms of cortisol are used to treat a variety of diseases.

Production and release

Cortisol is produced by the adrenal gland
Adrenal gland
In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...

 in the zona fasciculata, the second of three layers comprising the outer adrenal cortex
Adrenal cortex
Situated along the perimeter of the adrenal gland, the adrenal cortex mediates the stress response through the production of mineralocorticoids and glucocorticoids, including aldosterone and cortisol respectively. It is also a secondary site of androgen synthesis.-Layers:Notably, the reticularis in...

. This release is controlled by the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...

, a part of the brain. The secretion of corticotropin-releasing hormone (CRH)
Corticotropin-releasing hormone
Corticotropin-releasing hormone , originally named corticotropin-releasing factor , and also called corticoliberin, is a polypeptide hormone and neurotransmitter involved in the stress response...

 by the hypothalamus triggers anterior pituitary secretion of adrenocorticotropic hormone (ACTH). ACTH is carried by the blood to the adrenal cortex, where it triggers glucocorticoid secretion.

Main functions in the body

  • increasing blood sugar through gluconeogenesis
    Gluconeogenesis
    Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids....

  • suppressing the immune system
  • aiding in fat, protein, and carbohydrate metabolism


It suppresses the immune system by "muting" the white blood cells

Another function is to decrease bone formation. Cortisol is used to treat diseases such as Addison’s disease, 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
Eczema
Eczema is a form of dermatitis, or inflammation of the epidermis . In England, an estimated 5.7 million or about one in every nine people have been diagnosed with the disease by a clinician at some point in their lives.The term eczema is broadly applied to a range of persistent skin conditions...

 and others.

Cortisol prevents the release of substances in the body that cause inflammation. It stimulates gluconeogenesis (the breakdown of protein and fat to provide metabolites that can be converted to glucose in the liver) and it activates anti-stress and anti-inflammatory pathways.

Patterns

The amount of cortisol present in the blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....

 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
Sleep
Sleep is a naturally recurring state characterized by reduced or absent consciousness, relatively suspended sensory activity, and inactivity of nearly all voluntary muscles. It is distinguished from quiet wakefulness by a decreased ability to react to stimuli, and is more easily reversible than...

. Information about the light/dark cycle
Circadian rhythm
A circadian rhythm, popularly referred to as body clock, is an endogenously driven , roughly 24-hour cycle in biochemical, physiological, or behavioural processes. Circadian rhythms have been widely observed in plants, animals, fungi and cyanobacteria...

 is transmitted from the retina
Retina
The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...

 to the paired suprachiasmatic nuclei in the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...

. This pattern is not present at birth; estimates of when it begins vary from two weeks to nine months of age.

Changed patterns of serum cortisol levels have been observed in connection with abnormal ACTH levels, clinical depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...

, psychological stress, and physiological stressors such as hypoglycemia
Hypoglycemia
Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...

, illness, fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...

, trauma, surgery
Surgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...

, fear
Fear
Fear is a distressing negative sensation induced by a perceived threat. It is a basic survival mechanism occurring in response to a specific stimulus, such as pain or the threat of danger...

, pain
Pain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...

, physical exertion, or temperature
Temperature
Temperature is a physical property of matter that quantitatively expresses the common notions of hot and cold. Objects of low temperature are cold, while various degrees of higher temperatures are referred to as warm or hot...

 extremes. Cortisol levels may also differ for individuals with autism
Autism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...

 or Asperger's syndrome.

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

Normal levels

Reference ranges for blood plasma content of free cortisol
Time Lower limit Upper limit Unit
09:00 am  140 700 >-
| 5
25 >-
|rowspan=2| Midnight
80 350 >-
| 2.9
13


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 range
Reference range
In health-related fields, a reference range or reference interval usually describes the variations of a measurement or value in healthy individuals...

s for urinalysis
Urinalysis
A urinalysis , also known as Routine and Microscopy , is an array of tests performed on urine, and one of the most common methods of medical diagnosis...

 of free cortisol
Lower limit Upper limit Unit
28 or 30 280 or 490 nmol/24h
10 or 11 100 or 176 µg
Microgram
In the metric system, a microgram is a unit of mass equal to one millionth of a gram , or 1/1000 of a milligram. It is one of the smallest units of mass commonly used...

/24 h

A urinary value smaller than 200 nmol/24h (72 µg/24h) strongly indicates absence of Cushing's syndrome
Cushing's syndrome
Cushing's syndrome is a hormone disorder caused by high levels of cortisol in the blood. This can be caused by taking glucocorticoid drugs, or by tumors that produce cortisol or adrenocorticotropic hormone or CRH...

.

Effects

Cortisol is released in response to stress, acting to restore homeostasis
Homeostasis
Homeostasis is the property of a system that regulates its internal environment and tends to maintain a stable, constant condition of properties like temperature or pH...

. However, prolonged cortisol secretion (which may be due to chronic stress
Chronic stress
Chronic stress is the response to emotional pressure suffered for a prolonged period over which an individual perceives he or she has no control. It involves an endocrine system response in which occurs a release of corticosteroids...

 or the excessive secretion seen in Cushing's syndrome
Cushing's syndrome
Cushing's syndrome is a hormone disorder caused by high levels of cortisol in the blood. This can be caused by taking glucocorticoid drugs, or by tumors that produce cortisol or adrenocorticotropic hormone or CRH...

) results in significant physiological changes.

Insulin:
Cortisol counteracts insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....

, contributes to hyperglycemia-causing hepatic gluconeogenesis
Gluconeogenesis
Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids....

 and inhibits the peripheral utilization of glucose (insulin resistance
Insulin resistance
Insulin resistance is a physiological condition where the natural hormone insulin becomes less effective at lowering blood sugars. The resulting increase in blood glucose may raise levels outside the normal range and cause adverse health effects, depending on dietary conditions. Certain cell types...

) by decreasing the translocation of glucose transporter
Glucose transporter
Glucose transporters are a wide group of membrane proteins that facilitate the transport of glucose over a plasma membrane. Because glucose is a vital source of energy for all life these transporters are present in all phyla...

s (especially GLUT4
GLUT4
Glucose transporter type 4, also known as GLUT4, is a protein that in humans is encoded by the GLUT4 gene. GLUT4 is the insulin-regulated glucose transporter found in adipose tissues and striated muscle that is responsible for insulin-regulated glucose translocation into the cell...

) to the cell membrane. However, cortisol increases glycogen
Glycogen
Glycogen is a molecule that serves as the secondary long-term energy storage in animal and fungal cells, with the primary energy stores being held in adipose tissue...

 synthesis (glycogenesis
Glycogenesis
Glycogenesis is the process of glycogen synthesis, in which glucose molecules are added to chains of glycogen for storage. This process is activated during rest periods following the Cori cycle, in the liver, and also activated by insulin in response to high glucose levels, for example after a...

) in the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

. 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.

Collagen:
In laboratory rats, cortisol-induced collagen loss in the skin is ten times greater than in any other tissue. Cortisol (as opticortinol) may inversely inhibit IgA
IGA
Iga or IGA may stand for:-Given name:* a female given name of Polish origin. The name originates from the female given name Jadwiga and stands for gia,or gina in the USA....

 precursor cells in the intestines of calves. Cortisol also inhibits IgA in serum, as it does IgM
IGM
IGM as an acronym or abbreviation can refer to:* Immunoglobulin M , the primary antibody against A and B antigens on red blood cells* International Grandmaster, a chess ranking* intergalactic medium* Intragroup medium - see: Intracluster medium...

; however, it is not shown to inhibit IgE
IGE
IGE was one of the largest services company buying and selling virtual currencies and accounts for MMORPG. During its peak time, it had offices in Los Angeles, China , and headquarters & customer service centre in Hong Kong. IGE was one of the main monopoly in virtual economy services, also known...

.

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
Methylprednisolone
Methylprednisolone is a synthetic glucocorticoid or corticosteroid drug. It is marketed in the USA and Canada under the brand names Medrol and Solu-Medrol. It is also available as a generic drug....

).

Sodium:
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.

Potassium:
A sodium load augments the intense potassium excretion by cortisol; corticosterone
Corticosterone
Corticosterone is a 21-carbon steroid hormone of the corticosteroid type produced in the cortex of the adrenal glands.-Roles:In many species, including amphibians, reptiles, rodents and birds, corticosterone is a main glucocorticoid, involved in regulation of fuel, immune reactions, and stress...

 is comparable to cortisol in this case. In order for potassium to move out of the cell, cortisol moves an equal number of sodium ions into the cell. This should make pH
PH
In chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...

 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
Deoxycorticosterone
11-Deoxycorticosterone is a steroid hormone produced by the adrenal gland that possesses mineralocorticoid activity and acts as a precursor to aldosterone. As its names indicate, it can be understood as 21-hydroxy- variant of progesterone or a 11-deoxy- variant of corticosterone...

 effect). Nevertheless, cortisol consistently causes serum alkalosis
Alkalosis
Alkalosis refers to a condition reducing hydrogen ion concentration of arterial blood plasma . Generally, alkalosis is said to occur when pH of the blood exceeds 7.45. The opposite condition is acidosis .-Causes:...

; 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).

Water:
Cortisol acts as a diuretic 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.

Copper:
Cortisol stimulates many copper enzymes (often to 50% of their total potential), probably to increase copper availability for immune purposes. This includes lysyl oxidase, an enzyme which is used to cross-link collagen and elastin
Elastin
Elastin is a protein in connective tissue that is elastic and allows many tissues in the body to resume their shape after stretching or contracting. Elastin helps skin to return to its original position when it is poked or pinched. Elastin is also an important load-bearing tissue in the bodies of...

. Especially valuable for immune response is cortisol's stimulation of the superoxide dismutase
Superoxide dismutase
Superoxide dismutases are a class of enzymes that catalyze the dismutation of superoxide into oxygen and hydrogen peroxide. As such, they are an important antioxidant defense in nearly all cells exposed to oxygen...

, 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
Metallothionein
Metallothionein is a family of cysteine-rich, low molecular weight proteins. They are localized to the membrane of the Golgi apparatus...

 (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.

Immune system:
Cortisol can weaken the activity of the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...

. 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
Endotoxin
Endotoxins are toxins associated with some Gram-negative bacteria. An "endotoxin" is a toxin that is a structural molecule of the bacteria that is recognized by the immune system.-Gram negative:...

 bacteria have gained an advantage by forcing the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...

 to increase cortisol levels (forcing the secretion of CRH
Corticotropin-releasing hormone
Corticotropin-releasing hormone , originally named corticotropin-releasing factor , and also called corticoliberin, is a polypeptide hormone and neurotransmitter involved in the stress response...

 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
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...

, and skin
Skin
-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...

). Rapid administration of corticosterone
Corticosterone
Corticosterone is a 21-carbon steroid hormone of the corticosteroid type produced in the cortex of the adrenal glands.-Roles:In many species, including amphibians, reptiles, rodents and birds, corticosterone is a main glucocorticoid, involved in regulation of fuel, immune reactions, and stress...

 (the endogenous Type I and Type II receptor agonist) or RU28362
RU28362
RU28362 is a molecule which binds the glucocorticoid receptor but not the mineralocorticoid receptor ....

 (a specific Type II receptor agonist) to adrenalectomized animals induced changes in leukocyte distribution. Natural killer cell
Natural killer cell
Natural killer cells are a type of cytotoxic lymphocyte that constitute a major component of the innate immune system. NK cells play a major role in the rejection of tumors and cells infected by viruses...

s are not affected by cortisol.

Bone metabolism:
Cortisol reduces bone
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...

 formation, favoring long-term development of osteoporosis. It transports potassium
Potassium
Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...

 out of cells in exchange for an equal number of sodium
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...

 ions (see above). This can trigger the hyperkalemia
Hyperkalemia
Hyperkalemia refers to the condition in which the concentration of the electrolyte potassium in the blood is elevated...

 of metabolic shock from surgery. Cortisol also reduces calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...

 absorption in the intestine.

Memory:
Cortisol works with epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...

 (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
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...

; this damage results in impaired learning. Furthermore, it has been shown that cortisol inhibits memory retrieval of already stored information.

Additional effects:
  • Increases blood pressure
    Blood pressure
    Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...

     by increasing the sensitivity of the vasculature to epinephrine
    Epinephrine
    Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...

     and norepinephrine
    Norepinephrine
    Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...

    ; in the absence of cortisol, widespread vasodilation
    Vasodilation
    Vasodilation refers to the widening of blood vessels resulting from relaxation of smooth muscle cells within the vessel walls, particularly in the large arteries, smaller arterioles and large veins. The process is essentially the opposite of vasoconstriction, or the narrowing of blood vessels. When...

     occurs

  • Inhibits secretion of corticotropin-releasing hormone
    Corticotropin-releasing hormone
    Corticotropin-releasing hormone , originally named corticotropin-releasing factor , and also called corticoliberin, is a polypeptide hormone and neurotransmitter involved in the stress response...

     (CRH), resulting in feedback inhibition
    Negative feedback
    Negative feedback occurs when the output of a system acts to oppose changes to the input of the system, with the result that the changes are attenuated. If the overall feedback of the system is negative, then the system will tend to be stable.- Overview :...

     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

  • Causes the kidneys to produce hypotonic urine

  • 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
    Histamine
    Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...

     secretion and stabilizing lysosomal
    Lysosome
    thumb|350px|Schematic of typical animal cell, showing subcellular components. [[Organelle]]s: [[nucleoli]] [[cell nucleus|nucleus]] [[ribosomes]] [[vesicle |vesicle]] rough [[endoplasmic reticulum]]...

     membranes. Stabilization of lysosomal membranes prevents their rupture, preventing damage to healthy tissues

  • Stimulates hepatic detoxification by inducing tryptophan oxygenase (reducing serotonin
    Serotonin
    Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

     levels in the brain), glutamine synthase (reducing glutamate and ammonia
    Ammonia
    Ammonia is a compound of nitrogen and hydrogen with the formula . It is a colourless gas with a characteristic pungent odour. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia, either directly or...

     levels in the brain), cytochrome P-450 hemoprotein (mobilizing arachidonic acid
    Arachidonic acid
    Arachidonic acid is a polyunsaturated omega-6 fatty acid 20:4.It is the counterpart to the saturated arachidic acid found in peanut oil, Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6).It is the counterpart to the saturated arachidic acid found in peanut oil,...

    ), and metallothionein
    Metallothionein
    Metallothionein is a family of cysteine-rich, low molecular weight proteins. They are localized to the membrane of the Golgi apparatus...

     (reducing heavy metals
    Heavy metals
    A heavy metal is a member of a loosely-defined subset of elements that exhibit metallic properties. It mainly includes the transition metals, some metalloids, lanthanides, and actinides. Many different definitions have been proposed—some based on density, some on atomic number or atomic weight,...

     in the body)

  • In addition to cortisol's effects in binding to the glucocorticoid receptor
    Glucocorticoid receptor
    The glucocorticoid receptor also known as NR3C1 is the receptor to which cortisol and other glucocorticoids bind....

    , because of its molecular similarity to aldosterone
    Aldosterone
    Aldosterone is a hormone that increases the reabsorption of sodium ions and water and the release of potassium in the collecting ducts and distal convoluted tubule of the kidneys' functional unit, the nephron. This increases blood volume and, therefore, increases blood pressure. Drugs that...

     it also binds to the mineralocorticoid receptor
    Mineralocorticoid receptor
    The mineralocorticoid receptor , also known as the aldosterone receptor or nuclear receptor subfamily 3, group C, member 2, is a protein that in humans is encoded by the NR3C2 gene that is located on chromosome 4q31.1-31.2.MR is a receptor with high affinity for mineralocorticoids...

    . 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.

Binding

Most serum cortisol (all but about 4%) is bound to proteins, including corticosteroid binding globulin
Transcortin
Transcortin, also corticosteroid-binding globulin or CBG, is officially called serpin peptidase inhibitor, clade A , member 6.It is an alpha-globulin.-Binding:...

 (CBG) and serum albumin
Serum albumin
Serum albumin, often referred to simply as albumin is a protein that in humans is encoded by the ALB gene.Serum albumin is the most abundant plasma protein in mammals. Albumin is essential for maintaining the osmotic pressure needed for proper distribution of body fluids between intravascular...

. Free cortisol passes easily through cellular membranes, where they bind intracellular cortisol receptors.

Regulation

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
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...

. 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 for those diseases which gain an advantage by forcing the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...

 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) primarily affects 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
Corticosterone
Corticosterone is a 21-carbon steroid hormone of the corticosteroid type produced in the cortex of the adrenal glands.-Roles:In many species, including amphibians, reptiles, rodents and birds, corticosterone is a main glucocorticoid, involved in regulation of fuel, immune reactions, and stress...

, 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
    Magnesium
    Magnesium is a chemical element with the symbol Mg, atomic number 12, and common oxidation number +2. It is an alkaline earth metal and the eighth most abundant element in the Earth's crust and ninth in the known universe as a whole...

     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
    Interleukin
    Interleukins are a group of cytokines that were first seen to be expressed by white blood cells . The term interleukin derives from "as a means of communication", and "deriving from the fact that many of these proteins are produced by leukocytes and act on leukocytes"...

    -1 and -6 and enhancing the synthesis of interleukin-2; the former promotes higher CRH
    Corticotropin-releasing hormone
    Corticotropin-releasing hormone , originally named corticotropin-releasing factor , and also called corticoliberin, is a polypeptide hormone and neurotransmitter involved in the stress response...

     release. Omega 6 fatty acids, on the other hand, have an inverse effect on interleukin synthesis.
  • Music therapy
    Music therapy
    Music therapy is an allied health profession and one of the expressive therapies, consisting of an interpersonal process in which a trained music therapist uses music and all of its facets—physical, emotional, mental, social, aesthetic, and spiritual—to help clients to improve or maintain their...

     can reduce cortisol levels in certain situations.
  • Massage therapy can reduce cortisol.
  • Laughing, and the experience of humour, can lower cortisol levels.
  • Crying
    Crying
    Crying is shedding tears as a response to an emotional state in humans. The act of crying has been defined as "a complex secretomotor phenomenon characterized by the shedding of tears from the lacrimal apparatus, without any irritation of the ocular structures"...

     can reduce cortisol levels. William H. Frey II, a biochemist at the University of Minnesota
    University of Minnesota
    The University of Minnesota, Twin Cities is a public research university located in Minneapolis and St. Paul, Minnesota, United States. It is the oldest and largest part of the University of Minnesota system and has the fourth-largest main campus student body in the United States, with 52,557...

    , proposed that people feel "better" after crying, due to the elimination of hormones associated with stress
    Stress hormone
    Stress hormones such as cortisol, GH and norepinephrine are released at periods of high stress. The hormone regulating system is known as the endocrine system...

    , specifically adrenocorticotropic hormone
    Adrenocorticotropic hormone
    Adrenocorticotropic hormone , also known as 'corticotropin', 'Adrenocorticotrophic hormone', is a polypeptide tropic hormone produced and secreted by the anterior pituitary gland. It is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological...

    . This, paired with increased mucosal secretion during crying, could lead to a theory that crying is a mechanism developed in humans to dispose of this stress hormone when levels grow too high.
  • Soy-derived phosphatidylserine
    Phosphatidylserine
    Phosphatidylserine is a phospholipid component, usually kept on the inner-leaflet of cell membranes by an enzyme called flippase...

     interacts with cortisol; the correct dose, however, is unclear.
  • Vitamin C
    Vitamin C
    Vitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress...

     blunts cortisol release in response to mental and physical stressors.
  • Black tea
    Black tea
    Black tea is a variety of tea that is more oxidized than the oolong, green, and white varieties.All four varieties are made from leaves of the shrub Camellia sinensis. Black tea is generally stronger in flavor and contains more caffeine than the less oxidized teas. Two principal varieties of the...

     may hasten recovery from a high-cortisol condition.
  • Regular dancing to Argentine tango
    Argentine tango
    Argentine tango is a musical genre of simple quadruple metre and binary musical form, and the social dance that accompanies it. Its lyrics and music are marked by nostalgia, expressed through melodic instruments including the bandoneon. Originated at the ending of the 19th century in the suburbs of...

     has been shown to lead to significant decreases in salivary cortisol concentrations.
  • Sexual intercourse.

Factors generally increasing cortisol levels

  • Caffeine
    Caffeine
    Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...

     may increase cortisol levels.
  • Sleep deprivation
    Sleep deprivation
    Sleep deprivation is the condition of not having enough sleep; it can be either chronic or acute. A chronic sleep-restricted state can cause fatigue, daytime sleepiness, clumsiness and weight loss or weight gain. It adversely affects the brain and cognitive function. Few studies have compared the...

    .
  • Intense (high VO2 max
    VO2 max
    VO2 max is the maximum capacity of an individual's body to transport and use oxygen during incremental exercise, which reflects the physical fitness of the individual...

    ) or prolonged physical exercise
    Physical exercise
    Physical exercise is any bodily activity that enhances or maintains physical fitness and overall health and wellness. It is performed for various reasons including strengthening muscles and the cardiovascular system, honing athletic skills, weight loss or maintenance, as well as for the purpose of...

     stimulates cortisol release to increase gluconeogenesis
    Gluconeogenesis
    Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids....

     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.
  • Hypoestrogenism
    Hypoestrogenism
    Hypoestrogenism refers to a lower than normal level of estrogen, the primary sex hormone for women. In general, lower levels of estrogen may cause differences in the breasts, genitals, urinary tract and skin....

     and melatonin
    Melatonin
    Melatonin , also known chemically as N-acetyl-5-methoxytryptamine, is a naturally occurring compound found in animals, plants, and microbes...

     supplementation increase cortisol levels in postmenopausal women.
  • Burnout
    Burnout (psychology)
    Burnout is a psychological term for the experience of long-term exhaustion and diminished interest. Research indicates general practitioners have the highest proportion of burnout cases; according to a recent Dutch study in Psychological Reports, no less than 40% of these experienced high levels of...

     is associated with higher cortisol levels.
  • Severe trauma or stressful events can elevate cortisol levels in the blood for prolonged periods.
  • Subcutaneous adipose tissue regenerates cortisol from cortisone
    Cortisone
    Cortisone is a steroid hormone. It is one of the main hormones released by the adrenal gland in response to stress. In chemical structure, it is a corticosteroid closely related to corticosterone. It is used to treat a variety of ailments and can be administered intravenously, orally,...

    .
  • Anorexia nervosa
    Anorexia nervosa
    Anorexia nervosa is an eating disorder characterized by refusal to maintain a healthy body weight and an obsessive fear of gaining weight. Although commonly called "anorexia", that term on its own denotes any symptomatic loss of appetite and is not strictly accurate...

     may be associated with increased cortisol levels.
  • The serotonin
    Serotonin
    Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

     receptor gene 5HTR2C
    5-HT2C receptor
    The 5-HT2C receptor is a subtype of 5-HT receptor that binds the endogenous neurotransmitter serotonin . It is a G protein-coupled receptor that is coupled to Gq/G11 and mediates excitatory neurotransmission. HTR2C denotes the human gene encoding for the receptor, that in humans is located at the...

     is associated with increased cortisol production in men.
  • Oral contraceptive pills can increase cortisol levels in young women who perform whole-body-resistance exercise training. The effect of this may cause a reduction in the ability to gain muscle mass by weight training.
  • Commuting
    Commuting
    Commuting is regular travel between one's place of residence and place of work or full time study. It sometimes refers to any regular or often repeated traveling between locations when not work related.- History :...

     increases cortisol levels relative to the length of the trip, its predictability and the amount of effort involved.
  • Stimuli associated with sexual intercourse can increase cortisol levels in Gilts (a young female pig that has not produced her first litter) .

Clinical chemistry

  • Hypercortisolism: Excessive levels of cortisol in the blood. (See Cushing's syndrome
    Cushing's syndrome
    Cushing's syndrome is a hormone disorder caused by high levels of cortisol in the blood. This can be caused by taking glucocorticoid drugs, or by tumors that produce cortisol or adrenocorticotropic hormone or CRH...

    .)
  • Hypocortisolism (adrenal insufficiency
    Adrenal insufficiency
    Adrenal insufficiency is a condition in which the adrenal glands, located above the kidneys, do not produce adequate amounts of steroid hormones , primarily cortisol, but may also include impaired aldosterone production which regulates sodium, potassium and water retention...

    ): Insufficient levels of cortisol in the blood.


The relationship between cortisol and ACTH, and some consequent conditions, are as follows:
THE DISORDERS OF CORTISOL SECRETION
Plasma ACTH
Plasma Cortisol Primary hypercortisolism (Cushing's syndrome
Cushing's syndrome
Cushing's syndrome is a hormone disorder caused by high levels of cortisol in the blood. This can be caused by taking glucocorticoid drugs, or by tumors that produce cortisol or adrenocorticotropic hormone or CRH...

)
Secondary hypercortisolism (pituitary or ectopic tumor, Cushing's disease
Cushing's disease
Cushing's disease is a cause of Cushing's Syndrome characterised by increased secretion of adrenocorticotropic hormone from the anterior pituitary. This is most often as a result of a pituitary adenoma...

, pseudo-Cushing's syndrome
Pseudo-Cushing's syndrome
Pseudo-Cushing's syndrome is a medical condition in which patients display the signs, symptoms, and abnormal hormone levels seen in Cushing's syndrome...

)
Secondary hypocortisolism (pituitary tumor, Sheehan's syndrome
Sheehan's syndrome
Sheehan syndrome, also known as Simmonds' syndrome or postpartum hypopituitarism or postpartum pituitary necrosis, is hypopituitarism , caused by necrosis due to blood loss and hypovolemic shock during and after childbirth...

)
Primary hypocortisolism (Addison's disease
Addison's disease
Addison’s disease is a rare, chronic endocrine disorder in which the adrenal glands do not produce sufficient steroid hormones...

, Nelson's syndrome
Nelson's syndrome
Nelson's syndrome is the rapid enlargement of a pituitary adenoma that occurs after the removal of both adrenal glands.-Pathophysiology:Removal of both adrenal glands, or bilateral adrenalectomy, is an operation for Cushing's syndrome...

)


A 2010 study has found that serum cortisol predicts increased cardiovascular mortality in patients with acute coronary syndrome.

Pharmacology

Hydrocortisone is the pharmaceutical term for cortisol used in oral administration, intravenous injection or topical application. It is used as an immunosuppressive drug
Immunosuppressive drug
Immunosuppressive drugs or immunosuppressive agents are drugs that inhibit or prevent activity of the immune system. They are used in immunosuppressive therapy to:...

, given by injection in the treatment of severe allergic reactions such as anaphylaxis
Anaphylaxis
Anaphylaxis is defined as "a serious allergic reaction that is rapid in onset and may cause death". It typically results in a number of symptoms including throat swelling, an itchy rash, and low blood pressure...

 and angioedema
Angioedema
Angioedema or Quincke's edema is the rapid swelling of the dermis, subcutaneous tissue, mucosa and submucosal tissues. It is very similar to urticaria, but urticaria, commonly known as hives, occurs in the upper dermis...

, in place of prednisolone
Prednisolone
Prednisolone is the active metabolite of prednisone, which is also used as a drug.-Uses:Prednisolone is a corticosteroid drug with predominant glucocorticoid and low mineralocorticoid activity, making it useful for the treatment of a wide range of inflammatory and auto-immune conditions such as...

 in patients who need steroid treatment but cannot take oral medication, and perioperatively in patients on longterm steroid treatment to prevent Addisonian crisis
Addison's disease
Addison’s disease is a rare, chronic endocrine disorder in which the adrenal glands do not produce sufficient steroid hormones...

. It may be used topically for allergic rashes, eczema
Eczema
Eczema is a form of dermatitis, or inflammation of the epidermis . In England, an estimated 5.7 million or about one in every nine people have been diagnosed with the disease by a clinician at some point in their lives.The term eczema is broadly applied to a range of persistent skin conditions...

, psoriasis
Psoriasis
Psoriasis is an autoimmune disease that appears on the skin. It occurs when the immune system mistakes the skin cells as a pathogen, and sends out faulty signals that speed up the growth cycle of skin cells. Psoriasis is not contagious. However, psoriasis has been linked to an increased risk of...

 and certain other inflammatory skin conditions. It may also be injected into inflamed joints resulting from diseases such as gout
Gout
Gout is a medical condition usually characterized by recurrent attacks of acute inflammatory arthritis—a red, tender, hot, swollen joint. The metatarsal-phalangeal joint at the base of the big toe is the most commonly affected . However, it may also present as tophi, kidney stones, or urate...

.

Compared to hydrocortisone, prednisolone
Prednisolone
Prednisolone is the active metabolite of prednisone, which is also used as a drug.-Uses:Prednisolone is a corticosteroid drug with predominant glucocorticoid and low mineralocorticoid activity, making it useful for the treatment of a wide range of inflammatory and auto-immune conditions such as...

 is about four times as strong and dexamethasone
Dexamethasone
Dexamethasone is a potent synthetic member of the glucocorticoid class of steroid drugs. It acts as an anti-inflammatory and immunosuppressant...

 about forty times as strong, in their anti-inflammatory
Anti-inflammatory
Anti-inflammatory refers to the property of a substance or treatment that reduces inflammation. Anti-inflammatory drugs make up about half of analgesics, remedying pain by reducing inflammation as opposed to opioids, which affect the central nervous system....

 effect. For side effects, see corticosteroid
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...

 and prednisolone
Prednisolone
Prednisolone is the active metabolite of prednisone, which is also used as a drug.-Uses:Prednisolone is a corticosteroid drug with predominant glucocorticoid and low mineralocorticoid activity, making it useful for the treatment of a wide range of inflammatory and auto-immune conditions such as...

.

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
CortiSlim
CortiSlim is a weight loss, stress management and lifestyle product marketed worldwide since 2003 by Californian company CortiSlim International LLC. It is purported to enhance metabolism, de-stress, and support normal blood sugar levels...

 originally (and falsely) claimed that it contributed to weight loss by blocking cortisol. The manufacturer was fined $12 million by the Federal Trade Commission
Federal Trade Commission
The Federal Trade Commission is an independent agency of the United States government, established in 1914 by the Federal Trade Commission Act...

 in 2007 for false advertising
False advertising
False advertising or deceptive advertising is the use of false or misleading statements in advertising. As advertising has the potential to persuade people into commercial transactions that they might otherwise avoid, many governments around the world use regulations to control false, deceptive or...

, and no longer claims in their marketing that CortiSlim is a cortisol antagonist
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...

.

Biosynthesis

Cortisol is synthesized from cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...

. Synthesis takes place in the zona fasciculata
Zona fasciculata
The zona fasciculata constitutes the middle zone of the adrenal cortex, sitting directly beneath the zona glomerulosa. Constituent cells are organized into bundles or "fascicles"....

of the adrenal cortex
Adrenal cortex
Situated along the perimeter of the adrenal gland, the adrenal cortex mediates the stress response through the production of mineralocorticoids and glucocorticoids, including aldosterone and cortisol respectively. It is also a secondary site of androgen synthesis.-Layers:Notably, the reticularis in...

. (The name cortisol is derived from cortex.) While the adrenal cortex also produces aldosterone
Aldosterone
Aldosterone is a hormone that increases the reabsorption of sodium ions and water and the release of potassium in the collecting ducts and distal convoluted tubule of the kidneys' functional unit, the nephron. This increases blood volume and, therefore, increases blood pressure. Drugs that...

 (in the zona glomerulosa) and some sex hormones (in the zona reticularis), cortisol is its main secretion. 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
Anterior pituitary
A major organ of the endocrine system, the anterior pituitary, also called the adenohypophysis, is the glandular, anterior lobe of the pituitary gland...

 of the pituitary gland
Pituitary gland
In vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g , in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...

 with adrenocorticotropic hormone
Adrenocorticotropic hormone
Adrenocorticotropic hormone , also known as 'corticotropin', 'Adrenocorticotrophic hormone', is a polypeptide tropic hormone produced and secreted by the anterior pituitary gland. It is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological...

 (ACTH); ACTH production is in turn stimulated by corticotropin-releasing hormone
Corticotropin-releasing hormone
Corticotropin-releasing hormone , originally named corticotropin-releasing factor , and also called corticoliberin, is a polypeptide hormone and neurotransmitter involved in the stress response...

 (CRH), which is released by the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...

. 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).

Metabolism

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
    Cortisone
    Cortisone is a steroid hormone. It is one of the main hormones released by the adrenal gland in response to stress. In chemical structure, it is a corticosteroid closely related to corticosterone. It is used to treat a variety of ailments and can be administered intravenously, orally,...

     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
5-alpha reductase
5α-reductases, also known as 3-oxo-5α-steroid 4-dehydrogenases, are enzymes involved in steroid metabolism. They participate in 3 metabolic pathways: bile acid biosynthesis, androgen and estrogen metabolism, and prostate cancer....

 and 5-beta reductase are the rate-limiting factors
Rate-determining step
The rate-determining step is a chemistry term for the slowest step in a chemical reaction. The rate-determining step is often compared to the neck of a funnel; the rate at which water flows through the funnel is determined by the width of the neck, not by the speed at which water is poured in. In...

 respectively. 5-beta reductase is also the rate-limiting factor in the conversion of cortisone to tetrahydrocortisone
Tetrahydrocortisone
Tetrahydrocortisone is a steroid....

 (THE).

An alteration in 11-beta HSD1 has been suggested to play a role in the pathogenesis
Pathogenesis
The pathogenesis of a disease is the mechanism by which the disease is caused. The term can also be used to describe the origin and development of the disease and whether it is acute, chronic or recurrent...

 of obesity
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...

, hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...

, and insulin resistance
Insulin resistance
Insulin resistance is a physiological condition where the natural hormone insulin becomes less effective at lowering blood sugars. The resulting increase in blood glucose may raise levels outside the normal range and cause adverse health effects, depending on dietary conditions. Certain cell types...

 known as metabolic syndrome
Metabolic syndrome
Metabolic syndrome is a combination of medical disorders that, when occurring together, increase the risk of developing cardiovascular disease and diabetes. It affects one in five people in the United States and prevalence increases with age...

.

An alteration in 11-beta HSD2 has been implicated in essential hypertension
Essential hypertension
Essential hypertension is the form of hypertension that by definition, has no identifiable cause. It is the most common type of hypertension, affecting 95% of hypertensive patients, it tends to be familial and is likely to be the consequence of an interaction between environmental and genetic...

 and is known to lead to the syndrome of apparent mineralocorticoid excess (SAME).

External links

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