11-Deoxycortisol, also known as cortodoxone (

INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway; before the advent of motorized transportation they also provided accommo ...

), cortexolone as well as 17α,21-dihydroxyprogesterone or 17α,21-dihydroxypregn-4-ene-3,20-dione, is an

endogenous Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell. In contrast, exogenous substances and processes are those that originate from outside of an organism. For example, ...

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 verte ...

steroid hormone A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into two classes: corticosteroids (typically made in the adrenal cortex, hence ''cortico-'') and sex steroids (typically made in the gonads or placenta). With ...

, and a

metabolic intermediate Metabolic intermediates are molecules that are the precursors or metabolites of biologically significant molecules. Although these intermediates are of relatively minor direct importance to cellular function, they can play important roles in the a ...

towards

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

. It was first described by

Tadeusz Reichstein Tadeusz Reichstein (20 July 1897 – 1 August 1996) was a Polish-Swiss chemist and the Nobel Prize in Physiology or Medicine laureate (1950), which was awarded for his work on the isolation of cortisone. Early life Reichstein was born into a Pol ...

in 1938 as Substance S, thus has also been referred to as Reichstein's Substance S or Compound S.

Function

11-Deoxycortisol acts as a

, though is less potent than

. 11-Deoxycortisol is synthesized from 17α-hydroxyprogesterone by

21-hydroxylase Steroid 21-hydroxylase (also known as steroid 21-monooxygenase, cytochrome P450C21, 21α-hydroxylase and less commonly 21β-hydroxylase) is an enzyme that hydroxylates steroids at the C21 position and is involved in biosynthesis of aldosterone a ...

and is converted to

by 11β-hydroxylase. 11-Deoxycortisol in mammals has limited

biological activity In pharmacology, biological activity or pharmacological activity describes the beneficial or adverse effects of a drug on living matter. When a drug is a complex chemical mixture, this activity is exerted by the substance's active ingredient or ...

and mainly acts as

within the

pathway, leading to

. In

sea lamprey The sea lamprey (''Petromyzon marinus'') is a parasitic lamprey native to the Northern Hemisphere. It is sometimes referred to as the "vampire fish". Description The sea lamprey has an eel-like body without paired fins. Its mouth is jawless, ...

, a member of the agnathans that evolved more than 500 million years ago, 11-deoxycortisol is the major and final glucocorticoid, with mineralocorticoid activity. 11-deoxycortisol also takes part, by binding to specific corticosteroid receptors, in intestinal osmoregulation in sea lamprey at metamorphosis, during which they develop seawater tolerance before downstream migration. Sea lamprey do not have 11β-hydroxylase enzyme (CYP11B1) that converts 11-deoxycortisol to cortisol and

11-deoxycorticosterone 11-Deoxycorticosterone (DOC), or simply deoxycorticosterone, also known as 21-hydroxyprogesterone, as well as desoxycortone ( INN), deoxycortone, and cortexone, is a steroid hormone produced by the adrenal gland that possesses mineralocorticoi ...

corticosterone Corticosterone, also known as 17-deoxycortisol and 11β,21-dihydroxyprogesterone, is a 21-carbon steroid hormone of the corticosteroid type produced in the cortex of the adrenal glands. It is of minor importance in humans, except in the very ra ...

in mammals. This indicates that a complex and highly specific corticosteroid signaling pathway evolved at least 500 million years ago with the arrival of the earliest vertebrate. The absence of cortisol and corticosterone in sea lampreys suggests that the 11β-hydroxylase enzyme may not have been present early in vertebrate evolution.

Clinical significance

11-Deoxycortisol in mammals has limited glucocorticoid activity, but it is the direct precursor of the major mammalian glucocorticoid, cortisol. As a result, the level of 11-deoxycortisol is measured to diagnose impaired cortisol synthesis, to find out the enzyme deficiency that causes impairment along the pathway to cortisol, and to differentiate adrenal disorders. In 11β-hydroxylase deficiency, 11-deoxycortisol and

levels increase, and excess of

leads to

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 ...

-based hypertension (as opposed to 21-hydroxylase deficiency, in which patients have

low blood pressure Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...

from a lack of

s). In 11β-hydroxylase deficiency, 11-deoxycortisol can also be converted to

androstenedione Androstenedione, or 4-androstenedione (abbreviated as A4 or Δ4-dione), also known as androst-4-ene-3,17-dione, is an endogenous weak androgen steroid hormone and intermediate in the biosynthesis of estrone and of testosterone from dehy ...

in a pathway that could explain the increase in androstenedione levels this condition. In

deficiency, 11-deoxycortisol levels are low.

History

In 1934,

biochemist Biochemists are scientists who are trained in biochemistry. They study chemical processes and chemical transformations in living organisms. Biochemists study DNA, proteins and cell parts. The word "biochemist" is a portmanteau of "biological che ...

Tadeus Reichstein, working in Switzerland, began research on extracts from animal

adrenal glands The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex wh ...

in order to isolate physiologically active compounds. He was publishing results of his findings along the way. By 1944, he already isolated and elucidated the chemical structure of 29 pure substances. He was assigning names that consisted of the word "Substance" and a letter from the Latin alphabet to the newly found substances. In 1938, he has published an article about "Substance R" and "Substance S" describing their chemical structures and properties. The Substance S since about 1955 became known as 11-Deoxycortisol. In the 1930s and 1940s clinicians were discovering many uses for the newly discovered hormones, however, only minute quantities could be extracted from animal organs. Chemists were looking for production of these hormones on a larger industrial scale. In 1949, American research chemist

Percy Lavon Julian Percy Lavon Julian (April 11, 1899 – April 19, 1975) was an American research chemist and a pioneer in the chemical synthesis of medicinal drugs from plants. He was the first to synthesize the natural product physostigmine and was a pioneer in ...

, in looking for ways to produce

cortisone Cortisone is a pregnene (21-carbon) steroid hormone. It is a naturally-occurring corticosteroid metabolite that is also used as a pharmaceutical prodrug; it is not synthesized in the adrenal glands. Cortisol is converted by the action of the ...

, announced the synthesis of the Compound S, from the cheap and readily available

pregnenolone Pregnenolone (P5), or pregn-5-en-3β-ol-20-one, is an endogenous steroid and precursor/ metabolic intermediate in the biosynthesis of most of the steroid hormones, including the progestogens, androgens, estrogens, glucocorticoids, and minera ...

(synthesized from the soybean oil sterol

stigmasterol Stigmasterol – a plant sterol (''phytosterol'') – is among the most abundant of plant sterols, having a major function to maintain the structure and physiology of cell membranes. In the European Union, it is a food additive listed with E num ...

). On April 5, 1952,

Durey Peterson and

microbiologist A microbiologist (from Greek ) is a scientist who studies microscopic life forms and processes. This includes study of the growth, interactions and characteristics of microscopic organisms such as bacteria, algae, fungi, and some types of par ...

Herbert Murray at

Upjohn The Upjohn Company was a pharmaceutical manufacturing firm founded in 1886 in Hastings, Michigan, by Dr. William E. Upjohn who was an 1875 graduate of the University of Michigan medical school. The company was originally formed to make ''friabl ...

, published the first report of a breakthrough fermentation process for the microbial 11α-oxygenation of steroids (e.g.

progesterone Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the ma ...

) in a single step by common

mold A mold () or mould () is one of the structures certain fungi can form. The dust-like, colored appearance of molds is due to the formation of spores containing fungal secondary metabolites. The spores are the dispersal units of the fungi. Not ...

s of the order Mucorales. 11α-oxygenation of Compound S produces 11α-hydrocortisone, which can be chemically oxidized to

, or converted by further chemical steps to 11β-hydrocortisone (

References

{{DEFAULTSORT:Deoxycortisol, 11- Glucocorticoids Mineralocorticoids Pregnanes

Function

Clinical significance

History

See also

References