6β-Hydroxycortisol is an

endogenous Endogeny, in biology, refers to the property of originating or developing from within an organism, tissue, or cell. For example, ''endogenous substances'', and ''endogenous processes'' are those that originate within a living system (e.g. an ...

steroid A steroid is an organic compound with four fused compound, fused rings (designated A, B, C, and D) arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes t ...

. In humans, it is a

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

cortisol Cortisol is a steroid hormone in the glucocorticoid class of hormones and a stress hormone. When used as medication, it is known as hydrocortisone. Cortisol is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal corte ...

produced by

cytochrome p450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...

-3A

monooxygenase Monooxygenases are enzymes that incorporate one hydroxyl group (−OH) into substrates in many metabolic pathways. In this reaction, the two atoms of dioxygen are reduced to one hydroxyl group and one H2O molecule by the concomitant oxidation of ...

s, mainly, 6β-hydroxysteroid dehydrogenase (

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...

). 6β-hydroxycortisol is used as a biomarker of 6β-hydroxysteroid dehydrogenase (

) activity. Drugs that induce CYP3A4 may accelerate cortisol clearance, by accelerating cortisol conversion to 6β-hydroxycortisol, and vice versa: drugs that inhibit CYP3A4 can slow down cortisol clearance, as they reduce the conversion of cortisol to 6β-hydroxycortisol.

Biological role

Although the exact role of 6β-hydroxycortisol in the human body is not fully understood, it is believed to play an important role in the metabolism and clearance of cortisol. 6β-hydroxycortisol is a metabolite of cortisol: the enzyme 6β-hydroxysteroid dehydrogenase (CYP3A4) catalyzes the formation of 6β-hydroxycortisol from cortisol in the liver and other tissues; the resulting 6β-hydroxycortisol is excreted in urine. 6β-hydroxycortisol levels may be affected by drugs that induce or inhibit CYP3A4, thereby affecting cortisol metabolism.

Clinical significance

In normal metabolism, the level of 6β-hydroxycortisol is regulated by the activity of 6β-hydroxysteroid dehydrogenase (CYP3A4) and other enzymes involved in cortisol metabolism. Abnormal 6β-hydroxycortisol levels may indicate underlying metabolic abnormalities such as

Cushing's syndrome Cushing's syndrome is a collection of signs and symptoms due to prolonged exposure to glucocorticoids such as cortisol. Signs and symptoms may include high blood pressure, abdominal obesity but with thin arms and legs, reddish stretch marks, ...

, a condition characterized by overproduction of cortisol, or

Addison's disease Addison's disease, also known as primary adrenal insufficiency, is a rare long-term endocrine disorder characterized by inadequate production of the steroid hormones cortisol and aldosterone by the two outer layers of the cells of the adr ...

, a condition characterized by underproduction of cortisol. 6β-hydroxycortisol is being investigated as a potential biomarker of 6β-hydroxysteroid dehydrogenase (CYP3A4) activity and may have diagnostic or prognostic value in certain diseases. Understanding the role of 6β-hydroxycortisol in human physiology and disease may lead to the development of new diagnostic and therapeutic strategies. In addition to cortisol, many drugs are also metabolized by CYP3A4. Examples of drugs metabolized by CYP3A4 are

statin Statins (or HMG-CoA reductase inhibitors) are a class of medications that lower cholesterol. They are prescribed typically to people who are at high risk of cardiovascular disease. Low-density lipoprotein (LDL) carriers of cholesterol play ...

s (used to lower cholesterol levels),

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), colloquially known as "benzos", are a class of central nervous system (CNS) depressant, depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed t ...

s (used to treat anxiety and insomnia), calcium channel blockers (used to treat high blood pressure), etc. By measuring 6β-hydroxycortisol levels in clinical trials, researchers can assess whether certain drugs affect the activity CYP3A4 which is needed to metabolize other drugs and cortisol. Such observations bring knowledge about potentially dangerous drug interactions and help prevent life-threatening conditions in people who have impaired cortisol synthesis. One example of such dangerous interaction are

modafinil Modafinil, sold under the brand name Provigil among others, is a central nervous system (CNS) stimulant and wakefulness-promoting agent, eugeroic (wakefulness promoter) medication used primarily to treat narcolepsy, a sleep disorder characteri ...

(a stimulant) and

hydrocortisone Hydrocortisone is the name for the hormone cortisol when supplied as a medication. It is a corticosteroid and works as an anti-inflammatory and by immune suppression. Uses include conditions such as adrenocortical insufficiency, adrenogenit ...

(an exogenous cortisol). Modafinil has the ability to induce the activity of CYP3A4 which is involved in hydrocortisone clearance and consequently decrease the bioavailability of hydrocortisone.

References

{{DEFAULTSORT:Hydroxycortisol, 6β- Pregnanes Steroids

Biological role

Clinical significance

See also

References