AskDefine | Define cortisol

Dictionary Definition

cortisol n : an adrenal-cortex hormone (trade names Hydrocortone or Cortef) that is active in carbohydrate and protein metabolism [syn: hydrocortisone, Hydrocortone, Cortef]

User Contributed Dictionary

English

Noun

  1. The steroid hormone hydrocortisone.

Translations

the steroid hormone hydrocortisone
  • Czech: kortizol
  • Italian: cortisolo

Extensive Definition

Cortisol is a corticosteroid hormone produced by the Zona fasciculata of the adrenal cortex (in the adrenal gland). It is a vital hormone that is often referred to as the "stress hormone" as it is involved in the response to stress. It increases blood pressure, blood sugar levels and has an immunosuppressive action. In pharmacology, the synthetic form of cortisol is referred to as hydrocortisone, and is used as an antagonist in the treatment of allergies and inflammation as well as substitute supplementation in cortisol production deficiencies. When first introduced as a treatment for rheumatoid arthritis, it 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, 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.
There is also significant individual variation, although a given person tends to have consistent rhythms.
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. Its odd attributes all support this.
  • It increases blood pressure by increasing the sensitivity of the vasculature to epinephrine and norepinephrine. In the absence of cortisol, widespread vasodilation occurs.
  • 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.
  • 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 selictive 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 affect . 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

Diseases and disorders

  • Hypercortisolism: Excessive levels of cortisol in the blood result in Cushing's syndrome.
The relationship between cortisol and ACTH is as follows:

Pharmacology

Hydrocortisone is the chemical form of cortisol used for oral administration or intravenous injection. 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 inflamed joints resulting from diseases such as gout.
Compared to prednisolone, hydrocortisone is about 1/4 the strength for the anti-inflammatory effect, while Dexamethasone is about 40 times as strong as hydrocortisone. For side effects, see corticosteroid and prednisolone.
Hydrocortisone creams and ointments are available without prescription in strengths ranging from 0.5% to 2.5%, depending on local regulations, with stronger forms available with prescriptions only.
Advertising for the dietary supplement CortiSlim originally (and falsely) claimed that it contributed to weight loss by blocking cortisol. The manufacturer was fined $1.2 million by the Federal Trade Commission in 2007 for false advertising, and no longer claims in their marketing that CortiSlim is a cortisol antagonist.

Biochemistry

Biosynthesis

Cortisol is synthesized from cholesterol. The synthesis takes place in the zona fasciculata of the cortex of the adrenal glands. (The name cortisol comes 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. The medulla of the adrenal gland lies under the cortex and mainly secretes the catecholamines, adrenaline (epinephrine) and noradrenaline (norepinephrine) under sympathetic stimulation (more epinephrine is produced than norepinephrine, in a ratio 4:1).
The synthesis of cortisol in the adrenal gland is stimulated by the anterior lobe of the pituitary gland with adrenocorticotropic hormone (ACTH); production of ACTH is in turn stimulated by corticotropin-releasing hormone (CRH), released by the hypothalamus. ACTH increases the concentration of cholesterol in the inner mitochondrial membrane (via regulation of STAR (steroidogenic acute regulatory) protein). The cholesterol is converted to pregnenolone, catalysed by Cytochrome P450SCC (side chain cleavage).

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 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, while 11-beta HSD2 serves to decrease the local concentrations of biologically active cortisol. The CA3 area of hippocampus (memory) is affected by cortisol.
An alteration in 11-beta HSD1 has been suggested to play a role in the pathogenesis of obesity, hypertension, and insulin resistance, sometimes referred to the metabolic syndrome.
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).

Additional images

Image:11-Deoxycortisol.png|11-Deoxycortisol

References

External links

cortisol in German: Cortisol
cortisol in Spanish: Cortisol
cortisol in Esperanto: Kortisolo
cortisol in French: Cortisol
cortisol in Hebrew: קורטיזול
cortisol in Dutch: Cortisol
cortisol in Japanese: コルチゾール
cortisol in Norwegian: Kortisol
cortisol in Polish: Kortyzol
cortisol in Portuguese: Cortisol
cortisol in Slovenian: Kortizol
cortisol in Finnish: Kortisoli
cortisol in Swedish: Kortisol
cortisol in Turkish: Kortizol
cortisol in Chinese: 皮質醇
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