18-Oxocortisol 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 ...

, a metabolite of

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 ...

Clinical significance

18-Oxocortisol has been proposed as a biomarker for certain

diseases A disease is a particular abnormal condition that adversely affects the structure or function of all or part of an organism and is not immediately due to any external injury. Diseases are often known to be medical conditions that are asso ...

. In humans, 18-oxocortisol has no biological activity on

glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebra ...

mineralocorticoid Mineralocorticoids are a class of corticosteroids, which in turn are a class of steroid hormones. Mineralocorticoids are produced in the adrenal cortex and influence salt and water balances (electrolyte balance and fluid balance). The primary ...

receptors. In healthy subjects, the

biosynthesis Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme-Catalysis, catalyzed processes where chemical substances absorbed as nutrients (or previously converted through biosynthe ...

of 18-oxocortisol is low. The highest synthesis of 18-oxocortisol was found in certain cases of hypertension like in type 1

familial hyperaldosteronism Familial hyperaldosteronism is a group of inherited conditions in which the adrenal glands, which are small glands located on top of each kidney, produce too much of the hormone aldosterone. Excess aldosterone causes the kidneys to retain more ...

(glucocorticoid-curable hyperaldosteronism) and type 3

, where the adrenal glands are enlarged up to six times their normal size. Increased synthesis is also found in patients with aldosterone-producing

adenoma An adenoma is a benign tumor of epithelium, epithelial tissue with glandular origin, glandular characteristics, or both. Adenomas can grow from many glandular organ (anatomy), organs, including the adrenal glands, pituitary gland, thyroid, prosta ...

ACTH stimulation test The ACTH test (also called the cosyntropin, tetracosactide, or Synacthen test) is a medical test usually requested and interpreted by endocrinologists to assess the functioning of the adrenal glands' stress response by measuring the adrenal res ...

increases

urinary The human urinary system, also known as the urinary tract or renal system, consists of the kidneys, ureters, bladder, and the urethra. The purpose of the urinary system is to eliminate waste from the body, regulate blood volume and blood pressu ...

excretion Excretion is elimination of metabolic waste, which is an essential process in all organisms. In vertebrates, this is primarily carried out by the lungs, Kidney (vertebrates), kidneys, and skin. This is in contrast with secretion, where the substa ...

of 18-oxocortisol, and

dexamethasone Dexamethasone is a fluorinated glucocorticoid medication used to treat rheumatic problems, a number of skin diseases, severe allergies, asthma, chronic obstructive pulmonary disease (COPD), croup, brain swelling, eye pain following eye su ...

inhibits the excretion. The measurement of 18-oxocortisol using liquid chromatography tandem mass spectrometry has demonstrated its usefulness in distinguishing between unilateral and bilateral forms of primary aldosteronism. These measurements, along with measurements of

18-hydroxycortisol 18-Hydroxycortisol is an endogenous steroid, a metabolite of cortisol. Clinical significance 18-hydroxycortisol has been proposed as a biomarker for certain diseases. In humans, 18-hydroxycortisol has no biological activity on glucocorticoid or m ...

, provide a non-invasive method for diagnosing and classifying different subtypes of PA, potentially reducing the need for more invasive procedures like adrenal vein sampling. In aldosterone-producing adrenocortical adenoma (APA), which is the main cause of primary aldosteronism, the enzyme

aldosterone synthase Aldosterone synthase, also called steroid 18-hydroxylase, corticosterone 18-monooxygenase or P450C18, is a steroid hydroxylase cytochrome P450 enzyme involved in the biosynthesis of the mineralocorticoid aldosterone and other steroids. The enzym ...

(CYP11B2) plays a crucial role in

aldosterone Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays ...

production. Somatic mutations in genes like

KCNJ5 G protein-activated inward rectifier potassium channel 4 (GIRK-4) is a protein that in humans is encoded by the ''KCNJ5'' gene and is a type of G protein-gated ion channel. Function Potassium channels are present in most mammalian cells, wher ...

and CACNA1D can lead to an overexpression of CYP11B2 and increased production of aldosterone. CYP11B2 catalyzes the conversion of cortisol to 18-hydroxycortisol and then further converts it into 18-oxocortisol, making 18-oxocortisol a significant biomarker for diagnosing primary aldosteronism.

Biosynthesis

In patients with familial

hyperaldosteronism Hyperaldosteronism is a medical condition wherein too much aldosterone is produced. High aldosterone levels can lead to lowered levels of potassium in the blood (hypokalemia) and increased hydrogen ion excretion (alkalosis). Aldosterone is normal ...

type 1, there is a genetic crossover between specific regions of the CYP11B1 and CYP11B2 genes. This crossover results in the expression of an additional gene in the

zona fasciculata The ''zona fasciculata'' (sometimes, fascicular or fasciculate zone) constitutes the middle and also the widest zone of the adrenal cortex, sitting directly beneath the ''zona glomerulosa''. Constituent cells are organized into bundles or "fasc ...

, which is regulated by

ACTH Adrenocorticotropic hormone (ACTH; also adrenocorticotropin, corticotropin) is a polypeptide tropic hormone produced by and secreted by the anterior pituitary gland. It is also used as a medication and diagnostic agent. ACTH is an important ...

. The additional gene plays a role in synthesizing 18-oxocortisol by attaching the oxo (=O) functional group to carbon 18 of the steroid nucleus of cortisol. This additional gene also plays a role in the biosynthesis of

and

References

{{Endogenous steroids Pregnanes Steroids Mineralocorticoids

Clinical significance

Biosynthesis

See also

References