Cortisol is a corticosteroid hormone or glucocorticoid produced by zona fasciculata of the adrenal cortex, which is a part of the adrenal gland. It is usually referred to as the "stress hormone" as it is involved in response to stress and anxiety, controlled by CRH. It increases blood pressure and blood sugar, and reduces immune responses. Various synthetic forms of cortisol are used to treat a variety of different illnesses. The most well-known of these is a natural metabolic intermediary of cortisol called hydrocortisone. When first introduced as a treatment for rheumatoid arthritis, hydrocortisone was referred to as Compound E .
Physiology
The amount of cortisol present in the blood undergoes diurnal variation, with the highest levels present in the early morning, and the lowest levels present around midnight, or 3–5 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. The pattern is not present at birth (estimates of when it starts vary from two weeks to 9 months).
Changed patterns of serum cortisol levels have been observed in connection with abnormal ACTH levels, clinical depression, psychological stress, and such physiological stressors as hypoglycemia, illness, fever, trauma, surgery, fear, pain, physical exertion or extremes of temperature. Cortisol levels may also be different for people with autism or asperger's syndrome.
There is also significant individual variation, although a given person tends to have consistent rhythms.
Effects
In normal release, cortisol (like other glucocorticoid agents) has widespread actions which help restore homeostasis after stress. (These normal endogenous functions are the basis for the physiological consequences of chronic stress - prolonged cortisol secretion.). It has been proposed that its primary function is to inversely mobilize the immune system to fight potassium-depleting diarrhea diseases.
- It increases blood pressure by increasing the sensitivity of the vasculature to epinephrine and norepinephrine. In the absence of cortisol, widespread vasodilation occurs.
- It inhibits the 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.
- It allows for the kidneys to produce hypotonic urine.
- It has anti-inflammatory effects by reducing histamine secretion and stabilizing lysosomal membranes. The stabilization of lysosomal membranes prevents their rupture, thereby preventing damage to healthy tissues.
- It stimulates hepatic detoxification by inducing tryptophan oxygenase (to reduce serotonin levels in the brain), glutamine synthase (reduce glutamate and ammonia levels in the brain), cytochrome P-450 hemoprotein (mobilizes arachidonic acid), and metallothionein (reduces heavy metals in the body).
- In addition to the effects caused by cortisol binding to the glucocorticoid receptor, because of its molecular similarity to aldosterone, it also binds to the mineralocorticoid receptor. Aldosterone and cortisol have 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.
Binding
Most serum cortisol, all but about 4%, is bound to proteins including corticosteroid binding globulin ( CBG ), and serum albumin. Only free cortisol is available to most receptors.
Regulation
The primary control of cortisol is the pituitary gland peptide, adrenocorticotropic hormone (ACTH). ACTH probably controls cortisol by controlling 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 . 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 of which increase the amount of cortisol required to inhibit almost all the immune cells . Thus immune cells take over their own regulation, but at a higher cortisol set point. Even so, the rise of cortisol in diarrheic calves is minimal over healthy calves and drops below with time. The cells do not lose all of the fight or flight override because of interleukin-1's synergism with CRH. Cortisol even has a negative feedback effect on interleukin-1 which must be especially useful against those diseases which gain an advantage by forcing the hypothalamus to secrete too much CRH, such as the endotoxin bacteria..The suppressor immune cells are not affected by GRMF, so that the effective set point for the immune cells may be even higher than the set point for physiological processes. GRMF (called GAF in this reference) primarily affects the liver rather than the kidneys for some physiological processes .
A high potassium media, which stimulates aldosterone secretion in vitro, also stimulates cortisol secretion from the fasciculata zone of dog adrenals unlike corticosterone, upon which potassium has no effect . Potassium loading increases ACTH and cortisol in people also . This is no doubt the reason why a potassium deficiency causes cortisol to decline (as just mentioned) and why a potassium deficiency causes a decrease in conversion of 11deoxycortisol to cortisol . This probably contributes to the pain in rheumatoid arthritis since cell potassium is always low in that disease
Factors affecting cortisol levels
Factors generally reducing cortisol levels
- Magnesium supplementation decreases serum cortisol levels after aerobic exercise, but not in resistance training.
- Omega 3 fatty acids, in a dose dependent manner, can lower cortisol release influenced by mental stress by suppressing the synthesis of interleukin-1 and 6 and enhance the synthesis of interleukin-2, where the former promote higher CRH release. Omega 6 fatty acids, on the other hand, acts inversely on interleukin synthesis.
- Music therapy can reduce cortisol levels in certain situations.
- Massage therapy can reduce cortisol.
- Laughing and the experience of humour can lower cortisol levels.
- One study by a Japanese cosmetics company has asserted that makeup reduces cortisol levels in a mental stress situation.
- Soy derived Phosphatidylserine interacts with cortisol but the right dosage is still unclear.
- Vitamin C may slightly blunt cortisol release in response to a mental stressor.
- Black tea may speed up recovery from a high cortisol condition.
Factors generally increasing cortisol levels
- Caffeine may increase cortisol levels.
- Sleep deprivation increases cortisol levels.
- Intense (high VO2 max) or prolonged physical exercise stimulate cortisol release in order to increase gluconeogenesis and maintain blood glucose. Proper nutrition and high-level conditioning can help stabilize cortisol release.
- Val/Val variation of the BDNF gene in men, and the Val/Met variation in women is associated with increased salivary cortisol in a stressful situation.
- Hypoestrogenism and melatonin supplementation increases cortisol levels in postmenopausal women.
- Burnout is associated with higher cortisol levels.
- Severe trauma or stress events can elevate cortisol levels in the blood for prolonged periods.
- Subcutaneous adipose tissue regenerates cortisol from cortisone.
- Anorexia nervosa increases cortisol levels.
- The serotonin receptor gene 5HTR2C is associated with increased cortisol production in men.
- Some formulations of combined oral contraceptive pills increase cortisol levels in young women who perform whole-body resistance exercise training.
- Commuting increases cortisol levels, related to the length of the trip, the amount of effort involved and the predictability of the trip
Diseases and disorders
- Hypercortisolism : Excessive levels of cortisol in the blood.
- Hypocortisolism (adrenal insufficiency): Insufficient levels of cortisol in the blood.
The relationship between cortisol and ACTH, and some consequent conditions, are as follows:
Pharmacology
Hydrocortisone is the pharmaceutical term for cortisol used for 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 who need steroid treatment but cannot take oral medication, and peri-operatively in patients on long-term steroid treatment to prevent an Addisonian crisis. It may be used topically for allergic rashes, eczema, psoriasis and certain other inflammatory skin conditions. It may also be injected into
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