Cortisol

Cortisol is a corticosteroid hormone produced by the adrenal cortex that is involved in the response to stress; it increases blood pressure, blood sugar levels, may cause infertility in women, and suppresses the immune system. Synthetic cortisol, also known as hydrocortisone, is used as a drug mainly to fight allergies and inflammation.

Synthesis
Cortisol is synthesized from pregnenolone. The change involves hydroxylation of C-11, C-17, and C-21, the oxidation of C-3, and the isomerization of the C-5 double bond to C-4. The synthesis takes place in the zona fasciculata of the cortex of the adrenal glands. While the adrenal cortex produces aldosterone (in the zona glomerulosa) and some sex hormones (in the zona reticulosa), cortisol is its main secretion. (The name cortisol comes from cortex.) The medulla of the adrenal gland lies under the cortex and mainly secretes epinephrine and 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); production of ACTH is in turn stimulated by corticotropin-releasing hormone (CRH), released by the hypothalamus.

Physiology
The amount of cortisol present in the serum undergoes diurnal variation, with the highest levels present in the early morning, and lower levels in the evening, several 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. Changed patterns of serum cortisol levels have been observed in connection with abnormal ACTH levels, clinical depression, psychological stress, and such physiological stressors as hypoglycaemia, 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.

Cortisol also inhibits the secretion of corticotropin releasing hormone (CRH), resulting in feedback inhibition of ACTH secretion. Some researchers believe that this normal feedback system may break down when animals are exposed to chronic stress.

In normal release, cortisol has widespread actions which help restore homeostasis after stress. It acts as a physiological antagonist to insulin by promoting gluconeogenesis, breakdown of lipids, and proteins, and mobilization of extrahepatic amino acids and ketone bodies. This leads to increased blood glucose concentrations, resulting in increased glycogen formation in the liver (Freeman, 2002). It also increases blood pressure. The hormone lowers the activity of the immune system in the blood. It reflects leukocyte redistribution to lymph nodes, bone marrow, and skin (Cohen, 1972; Cox & Ford, 1982; Dhabhar & McEwen, 1996; Dhabhar and Dhabhar; Fauci, 1975; Fauci & Dale, 1974; Fauci & Dale, 1975; Yu et al., 1974). Acute 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. Bone formation is also lowered by cortisol.

These normal endogenous functions are the basis for the physiological consequences of chronic stress - prolonged cortisol secretion causes muscle wastage, hyperglycaemia, and suppresses immune / inflammatory responses. The same consequences arise from long-term use of glucocorticoid drugs.

Also, long-term exposure to cortisol results in damage to cells in the hippocampus. This damage results in impaired learning. However, short-term exposure of cortisol helps to create memories; this is the proposed mechanism for storage of flash bulb memories.

Most serum cortisol, all but about 4%, is bound to proteins including corticosteroid binding globulin (CBG), and albumin. Only free cortisol is available to most receptors.

THE DISORDERS OF CORTISOL SECRETION  Plasma Cortisol Plasma ACTH
Primary Hypercortisolism ↑ ↓
Secondary Hypercortisolism ( pituitary, Cushing Disease ) ↑ ↑
Primary Hypocortisolism ( Addison Disease ) ↓ ↑
Secondary Hypocortisolism ( pituitary ) ↓ ↓

Pharmacology
As an oral or injectable drug, cortisol is also known as hydrocortisone. 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 is given by topical application for its anti-inflammatory effect in allergic rashes, eczema and certain other inflammatory conditions. Brand names include Emocort®, Epifoam®, Sigmacort®, Hyderm®, NovoHydrocort® Cortoderm®, Cortizone-10®, Cortaid®, and Lanacort®

It may also be injected into inflamed joints resulting from diseases such as gout.

Compared to prednisolone, hydrocortisone is about 1/4th the strength. Dexamethasone is about 40 times stronger than hydrocortisone. For side effects, see corticosteroid and prednisolone.

Diseases
Hypercortisolism: Excessive levels of cortisol in the blood result in Cushing's syndrome.
Hypocortisolism, or adrenal insufficiency: If on the other hand the adrenal glands do not produce sufficient amounts of cortisol, Addison's disease is the consequence.

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