21-Deoxycortisol

Last updated

Contents

21-Deoxycortisol
21-Deoxycortisol.svg
Names
IUPAC name
11β,17α-Dihydroxypregn-4-ene-3,20-dione
Systematic IUPAC name
(1R,3aS,3bS,9aR,9bS,10S,11aS)-1-Acetyl-1,10-dihydroxy-9a,11a-dimethyl-1,2,3,3a,3b,4,5,8,9,9a,9b,10,11,11a-tetradecahydro-7H-cyclopenta[a]phenanthren-7-one
Other names
21-Desoxycortisol; 21-Dehydrohydrocortisone; 21-Deoxyhydrocortisone; 11β,17α-Dihydroxyprogesterone
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
KEGG
PubChem CID
UNII
  • InChI=1S/C21H30O4/c1-12(22)21(25)9-7-16-15-5-4-13-10-14(23)6-8-19(13,2)18(15)17(24)11-20(16,21)3/h10,15-18,24-25H,4-9,11H2,1-3H3/t15-,16-,17-,18+,19-,20-,21-/m0/s1
    Key: LCZBQMKVFQNSJR-UJPCIWJBSA-N
  • CC(=O)[C@]1(CC[C@@H]2[C@@]1(C[C@@H]([C@H]3[C@H]2CCC4=CC(=O)CC[C@]34C)O)C)O
Properties
C21H30O4
Molar mass 346.467 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

21-Deoxycortisol, also known as 11β,17α-dihydroxyprogesterone or as 11β,17α-dihydroxypregn-4-ene-3,20-dione, is a naturally occurring, endogenous steroid related to cortisol (11β,17α,21-trihydroxyprogesterone) which is formed as a metabolite from 17α-hydroxyprogesterone via 11β-hydroxylase. [1]

Marker of 21-hydroxylase deficiency

21-deoxycortisol is a marker of congenital adrenal hyperplasia due to 21-hydroxylase deficiency, [2] [1] [3] even in mild (non-classic) cases. [4] [5] It can be also used for newborn screening. [6]

The deficiency of the 21-hydroxylase enzyme leads to excess of 17α-hydroxyprogesterone, [7] [8] a 21-carbon (C21) steroid. This excess is accompanied by the accumulation of other C21 steroids, such as 21-deoxycortisol, which is formed by the 11β-hydroxylation of 17α-hydroxyprogesterone [7] via 11β-hydroxylase (CYP11B1). [1] The build-up of 21-deoxycortisol in patients with congenital adrenal hyperplasia have been described since at least 1955, this steroid was then called "21-desoxyhydrocortisone". [9] [10] Unlike 17α-hydroxyprogesterone, 21-deoxycortisol is not produced in the gonads and is uniquely adrenal-derived. Hence, 21-deoxycortisol is a more specific biomarker of 21-hydroxylase deficiency than is 17α-hydroxyprogesterone. [11]

The corticosteroid activity of 21-deoxycortisol is lower than that of cortisol. [12] [13]

As 21-deoxycortisol can be at high levels in congenital adrenal hyperplasia, and it has structural similarity to cortisol, it can cross-react in immunoassays, [14] [15] [16] resulting in a falsely normal or high cortisol result, when the true cortisol is actually low. Whereas immunoassays can suffer from cross-reactivity due to interactions with structural analogues, the selectivity offered by liquid chromatography-tandem mass spectrometry (LC-MS/MS) has largely overcome these limitations. [17] [18] [19] Hence, the use of LC-MS/MS instead of immunoassays in cortisol measurement aims to provide greater specificity. [20]

Besides 21-deoxycortisol, another C21 steroid, 21-deoxycorticosterone (11β-hydroxyprogesterone), has been proposed as a marker for 21-hydroxylase deficiency, [21] [22] [23] but this marker did not gain acceptance due to the fact that testing for the levels of this steroid is not routinely offered by diagnostic laboratories. [24]

See also

Related Research Articles

<span class="mw-page-title-main">Congenital adrenal hyperplasia</span> Medical condition

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders characterized by impaired cortisol synthesis. It results from the deficiency of one of the five enzymes required for the synthesis of cortisol in the adrenal cortex. Most of these disorders involve excessive or deficient production of hormones such as glucocorticoids, mineralocorticoids, or sex steroids, and can alter development of primary or secondary sex characteristics in some affected infants, children, or adults. It is one of the most common autosomal recessive disorders in humans.

<span class="mw-page-title-main">Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency</span> Medical condition

Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is a form of congenital adrenal hyperplasia (CAH) which produces a higher than normal amount of androgen, resulting from a defect in the gene encoding the enzyme steroid 11β-hydroxylase (11β-OH) which mediates the final step of cortisol synthesis in the adrenal. 11β-OH CAH results in hypertension due to excessive mineralocorticoid effects. It also causes excessive androgen production both before and after birth and can virilize a genetically female fetus or a child of either sex.

<span class="mw-page-title-main">Congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase deficiency</span> Medical condition

Congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase deficiency is an uncommon form of congenital adrenal hyperplasia (CAH) resulting from a mutation in the gene for one of the key enzymes in cortisol synthesis by the adrenal gland, 3β-hydroxysteroid dehydrogenase (3β-HSD) type II (HSD3B2). As a result, higher levels of 17α-hydroxypregnenolone appear in the blood with adrenocorticotropic hormone (ACTH) challenge, which stimulates adrenal corticosteroid synthesis.

Congenital adrenal hyperplasia due to 17α-hydroxylase deficiency is an uncommon form of congenital adrenal hyperplasia (CAH) resulting from a mutation in the gene CYP17A1, which produces the enzyme 17α-hydroxylase. It causes decreased synthesis of cortisol and sex hormones, with resulting increase in mineralocorticoid production. Thus, common symptoms include mild cortisol deficiency, ambiguous genitalia in men or amenorrhea at puberty in women, and hypokalemic hypertension. However, partial (incomplete) deficiency often has inconsistent symptoms between patients, and affected women may be asymptomatic except for infertility.

<span class="mw-page-title-main">Congenital adrenal hyperplasia due to 21-hydroxylase deficiency</span> Medical condition

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) is a genetic disorder characterized by impaired production of cortisol in the adrenal glands.

<span class="mw-page-title-main">17α-Hydroxyprogesterone</span> Chemical compound

17α-Hydroxyprogesterone (17α-OHP), also known as 17-OH progesterone (17-OHP), or hydroxyprogesterone (OHP), is an endogenous progestogen steroid hormone related to progesterone. It is also a chemical intermediate in the biosynthesis of many other endogenous steroids, including androgens, estrogens, glucocorticoids, and mineralocorticoids, as well as neurosteroids.

<span class="mw-page-title-main">17α-Hydroxypregnenolone</span> Chemical compound

17α-Hydroxypregnenolone is a pregnane (C21) steroid that is obtained by hydroxylation of pregnenolone at the C17α position. This step is performed by the mitochondrial cytochrome P450 enzyme 17α-hydroxylase (CYP17A1) that is present in the adrenal and gonads. Peak levels are reached in humans at the end of puberty and then decline. High levels are also achieved during pregnancy. It is also a known neuromodulator.

<span class="mw-page-title-main">11-Deoxycorticosterone</span> Chemical compound

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 mineralocorticoid activity and acts as a precursor to aldosterone. It is an active (Na+-retaining) mineralocorticoid. As its names indicate, 11-deoxycorticosterone can be understood as the 21-hydroxy-variant of progesterone or as the 11-deoxy-variant of corticosterone.

<span class="mw-page-title-main">Aldosterone synthase</span> Protein-coding gene in the species Homo sapiens

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 enzyme catalyzes sequential hydroxylations of the steroid angular methyl group at C18 after initial 11β-hydroxylation. It is encoded by the CYP11B2 gene in humans.

<span class="mw-page-title-main">CYP17A1</span> Mammalian protein found in Homo sapiens

Cytochrome P450 17A1 is an enzyme of the hydroxylase type that in humans is encoded by the CYP17A1 gene on chromosome 10. It is ubiquitously expressed in many tissues and cell types, including the zona reticularis and zona fasciculata of the adrenal cortex as well as gonadal tissues. It has both 17α-hydroxylase and 17,20-lyase activities, and is a key enzyme in the steroidogenic pathway that produces progestins, mineralocorticoids, glucocorticoids, androgens, and estrogens. More specifically, the enzyme acts upon pregnenolone and progesterone to add a hydroxyl (-OH) group at carbon 17 position (C17) of the steroid D ring, or acts upon 17α-hydroxyprogesterone and 17α-hydroxypregnenolone to split the side-chain off the steroid nucleus.

<span class="mw-page-title-main">21-Hydroxylase</span> Human enzyme that hydroxylates steroids

Steroid 21-hydroxylase is a protein that in humans is encoded by the CYP21A2 gene. The protein is an enzyme that hydroxylates steroids at the C21 position on the molecule. Naming conventions for enzymes are based on the substrate acted upon and the chemical process performed. Biochemically, this enzyme is involved in the biosynthesis of the adrenal gland hormones aldosterone and cortisol, which are important in blood pressure regulation, sodium homeostasis and blood sugar control. The enzyme converts progesterone and 17α-hydroxyprogesterone into 11-deoxycorticosterone and 11-deoxycortisol, respectively, within metabolic pathways which in humans ultimately lead to aldosterone and cortisol creation—deficiency in the enzyme may cause congenital adrenal hyperplasia.

<span class="mw-page-title-main">Steroid 11β-hydroxylase</span> Protein found in mammals

Steroid 11β-hydroxylase, also known as steroid 11β-monooxygenase, is a steroid hydroxylase found in the zona glomerulosa and zona fasciculata of the adrenal cortex. Named officially the cytochrome P450 11B1, mitochondrial, it is a protein that in humans is encoded by the CYP11B1 gene. The enzyme is involved in the biosynthesis of adrenal corticosteroids by catalyzing the addition of hydroxyl groups during oxidation reactions.

<span class="mw-page-title-main">11-Deoxycortisol</span> Chemical compound

11-Deoxycortisol, also known as cortodoxone (INN), cortexolone as well as 17α,21-dihydroxyprogesterone or 17α,21-dihydroxypregn-4-ene-3,20-dione, is an endogenous glucocorticoid steroid hormone, and a metabolic intermediate toward cortisol. It was first described by Tadeusz Reichstein in 1938 as Substance S, thus has also been referred to as Reichstein's Substance S or Compound S.

<span class="mw-page-title-main">Inborn errors of steroid metabolism</span> Medical condition

An inborn error of steroid metabolism is an inborn error of metabolism due to defects in steroid metabolism.

Maria Iandolo New is a professor of Pediatrics, Genomics and Genetics at Icahn School of Medicine at Mount Sinai in New York City. She is an expert in congenital adrenal hyperplasia (CAH), a genetic condition affecting the adrenal gland that can affect sexual development.

<span class="mw-page-title-main">11β-Hydroxyprogesterone</span> Chemical compound

11β-Hydroxyprogesterone (11β-OHP), also known as 21-deoxycorticosterone, as well as 11β-hydroxypregn-4-ene-3,20-dione, is a naturally occurring, endogenous steroid and derivative of progesterone. It is a potent mineralocorticoid. Syntheses of 11β-OHP from progesterone is catalyzed by the steroid 11β-hydroxylase (CYP11B1) enzyme, and, to a lesser extent, by the aldosterone synthase enzyme (CYP11B2).

<span class="mw-page-title-main">21-Deoxycortisone</span> Chemical compound

21-Deoxycortisone, also known as 21-desoxycortisone, 11-keto-17α-hydroxyprogesterone, or 17α-hydroxypregn-4-ene-3,11,20-trione, is a naturally occurring, endogenous steroid and minor intermediate and metabolite in corticosteroid metabolism. It is related to 21-deoxycortisol (11β,17α-dihydroxyprogesterone) and is reversibly formed from it by 11β-hydroxysteroid dehydrogenase, analogously to the reversible formation of cortisone from cortisol. 21-Deoxycortisone can be transformed into cortisone by 21-hydroxylase.

Late onset congenital adrenal hyperplasia (LOCAH), also known as nonclassic congenital adrenal hyperplasia, is a milder form of congenital adrenal hyperplasia (CAH), a group of autosomal recessive disorders characterized by impaired cortisol synthesis that leads to variable degrees of postnatal androgen excess.

<span class="mw-page-title-main">Androgen backdoor pathway</span> Series of interconnected biochemical reactions

The androgen backdoor pathway synthesizes physiologically relevant androgens from 21-carbon steroids (pregnanes) via 5α-reduction, bypassing testosterone. This differs from the conventional, canonical androgenic pathway, which involves testosterone.

<span class="mw-page-title-main">5α-Pregnane-3α,17α-diol-20-one</span> Chemical compound

5α-Pregnane-3α,17α-diol-20-one, also known as 17α-hydroxyallopregnanolone (17-OH-allo) is an endogenous steroid.

References

  1. 1 2 3 Cristoni S, Cuccato D, Sciannamblo M, Bernardi LR, Biunno I, Gerthoux P, Russo G, Weber G, Mora S (2004). "Analysis of 21-deoxycortisol, a marker of congenital adrenal hyperplasia, in blood by atmospheric pressure chemical ionization and electrospray ionization using multiple reaction monitoring". Rapid Commun. Mass Spectrom. 18 (1): 77–82. Bibcode:2004RCMS...18...77C. doi:10.1002/rcm.1284. PMID   14689562.
  2. ↑ Greaves RF, Kumar M, Mawad N, Francescon A, Le C, O'Connell M, Chi J, Pitt J (October 2023). "Best Practice for Identification of Classical 21-Hydroxylase Deficiency Should Include 21 Deoxycortisol Analysis with Appropriate Isomeric Steroid Separation". Int J Neonatal Screen. 9 (4): 58. doi: 10.3390/ijns9040058 . PMC   10594498 . PMID   37873849.
  3. ↑ Miller WL (2019). "Congenital Adrenal Hyperplasia: Time to Replace 17OHP with 21-Deoxycortisol". Hormone Research in Paediatrics. 91 (6): 416–420. doi: 10.1159/000501396 . PMID   31450227. S2CID   201733086.
  4. ↑ Ng JL, Lim EM, Zhang R, Beilby JP, Watts GF, Brown SJ, Stuckey BGA (June 2023). "Serum 21-deoxycortisol for diagnosis of non-classic congenital adrenal hyperplasia in women with androgen excess". J Clin Endocrinol Metab. 108 (12): e1560–e1570. doi: 10.1210/clinem/dgad377 . PMC   10655544 . PMID   37358001. S2CID   259249719.
  5. ↑ Oriolo C, Fanelli F, Castelli S, Mezzullo M, Altieri P, Corzani F, Pelusi C, Repaci A, Di Dalmazi G, Vicennati V, Baldazzi L, Menabò S, Dormi A, Nardi E, Brillanti G, Pasquali R, Pagotto U, Gambineri A (2020). "Steroid biomarkers for identifying non-classic adrenal hyperplasia due to 21-hydroxylase deficiency in a population of PCOS with suspicious levels of 17OH-progesterone". Journal of Endocrinological Investigation. 43 (10): 1499–1509. doi:10.1007/s40618-020-01235-3. PMID   32236851. S2CID   214715756.
  6. ↑ Held PK, Bialk ER, Lasarev MR, Allen DB (March 2022). "21-Deoxycortisol is a Key Screening Marker for 21-Hydroxylase Deficiency". J Pediatr. 242: 213–219.e1. doi:10.1016/j.jpeds.2021.10.063. PMID   34780778. S2CID   244106268.
  7. 1 2 Turcu AF, Rege J, Chomic R, Liu J, Nishimoto HK, Else T, Moraitis AG, Palapattu GS, Rainey WE, Auchus RJ (2015). "Profiles of 21-Carbon Steroids in 21-hydroxylase Deficiency". The Journal of Clinical Endocrinology and Metabolism. 100 (6): 2283–2290. doi:10.1210/jc.2015-1023. PMC   4454804 . PMID   25850025.
  8. ↑ Speiser PW, Arlt W, Auchus RJ, Baskin LS, Conway GS, Merke DP, et al. (November 2018). "Congenital Adrenal Hyperplasia Due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline". The Journal of Clinical Endocrinology and Metabolism. 103 (11): 4043–4088. doi:10.1210/jc.2018-01865. PMC   6456929 . PMID   30272171.
  9. ↑ JAILER JW, GOLD JJ, VANDE WIELE R, LIEBERMAN S (1955). "17alpha-hydroxyprogesterone and 21-desoxyhydrocortisone; their metabolism and possible role in congenital adrenal virilism". The Journal of Clinical Investigation. 34 (11): 1639–46. doi:10.1172/JCI103217. PMC   438744 . PMID   13271547.
  10. ↑ El-Farhan N, Rees DA, Evans C (May 2017). "Measuring cortisol in serum, urine and saliva - are our assays good enough?". Annals of Clinical Biochemistry. 54 (3): 308–322. doi: 10.1177/0004563216687335 . PMID   28068807. S2CID   206397561.
  11. ↑ Merke DP, Auchus RJ (September 2020). "Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency". The New England Journal of Medicine. 383 (13): 1248–1261. doi:10.1056/NEJMra1909786. PMID   32966723. S2CID   221884108.
  12. ↑ Endocrine Pharmacology: Physiological Basis and Therapeutic Applications. CUP Archive. 1980. pp. 158–. ISBN   978-0-521-22673-8.
  13. ↑ Engels M, Pijnenburg-Kleizen KJ, Utari A, Faradz SM, Oude-Alink S, van Herwaarden AE, Span PN, Sweep FC, Claahsen-van der Grinten HL (November 2019). "Glucocorticoid Activity of Adrenal Steroid Precursors in Untreated Patients With Congenital Adrenal Hyperplasia". The Journal of Clinical Endocrinology and Metabolism. 104 (11): 5065–5072. doi: 10.1210/jc.2019-00547 . PMID   31090904.
  14. ↑ Winter WE, Bazydlo L, Harris NS (2012). "Cortisol - Clinical Indications and Laboratory Testing". AACC Clinical Laboratory News. Archived from the original on 4 January 2018.
  15. ↑ Krasowski MD, Drees D, Morris CS, Maakestad J, Blau JL, Ekins S (2014). "Cross-reactivity of steroid hormone immunoassays: clinical significance and two-dimensional molecular similarity prediction". BMC Clinical Pathology. 14 (33): 33. doi: 10.1186/1472-6890-14-33 . PMC   4112981 . PMID   25071417.
  16. ↑ Agrawal N, Chakraborty PP, Sinha A, Maiti A (2020). "False elevation of serum cortisol in chemiluminescence immunoassay by Siemens Advia Centaur XP system in 21-hydroxylase deficiency: An 'endocrine laboma'". BMJ Case Reports. 13 (9): e235450. doi:10.1136/bcr-2020-235450. PMC   7477984 . PMID   32900728. S2CID   221567576.
  17. ↑ Tiulpakov MA, Nagaeva EV, Kalinchenko NY, Bezlepkina OB (January 2024). "[A promising approach for therapy control in congenital adrenal hyperplasia. Problems of Endocrinology]". Probl Endokrinol (Mosk) (in Russian). 69 (6): 102–108. doi:10.14341/probl13328. PMC   10848187 . PMID   38311999.
  18. ↑ Kurtoğlu S, Hatipoğlu N (7 March 2017). "Non-Classical Congenital Adrenal Hyperplasia in Childhood". Journal of Clinical Research in Pediatric Endocrinology. 9 (1): 1–7. doi:10.4274/jcrpe.3378. PMC   5363159 . PMID   27354284.
  19. ↑ Hawley JM, Keevil BG (September 2016). "Endogenous glucocorticoid analysis by liquid chromatography-tandem mass spectrometry in routine clinical laboratories". The Journal of Steroid Biochemistry and Molecular Biology. 162: 27–40. doi:10.1016/j.jsbmb.2016.05.014. PMID   27208627. S2CID   206501499.
  20. ↑ D'aurizio F, Cantù M (September 2018). "Clinical endocrinology and hormones quantitation: the increasing role of mass spectrometry". Minerva Endocrinologica. 43 (3): 261–284. doi:10.23736/S0391-1977.17.02764-X. PMID   29083134. S2CID   12984040.
  21. ↑ Gueux B, Fiet J, Galons H, Boneté R, Villette J, Vexiau P, Pham-Huu-Trung M, Raux-Eurin M, Gourmelen M, Brérault J, Julien R, Dreux C (1987). "The measurement of 11 beta-hydroxy-4-pregnene-3,20-dione (21-deoxycorticosterone) by radioimmunoassay in human plasma". Journal of Steroid Biochemistry. 26 (1): 145–50. doi:10.1016/0022-4731(87)90043-4. PMID   3546944.
  22. ↑ Fiet J, Gueux B, Rauxdemay M, Kuttenn F, Vexiau P, Brerault J, Couillin P, Galons H, Villette J, Julien R, Dreux C (1989). "Increased plasma 21-deoxycorticosterone (21-DB) levels in late-onset adrenal 21-hydroxylase deficiency suggest a mild defect of the mineralocorticoid pathway". The Journal of Clinical Endocrinology and Metabolism. 68 (3): 542–7. doi:10.1210/jcem-68-3-542. PMID   2537337.
  23. ↑ Fiet J, Le Bouc Y, Guéchot J, Hélin N, Maubert MA, Farabos D, Lamazière A (2017). "A Liquid Chromatography/Tandem Mass Spectometry [sic] Profile of 16 Serum Steroids, Including 21-Deoxycortisol and 21-Deoxycorticosterone, for Management of Congenital Adrenal Hyperplasia". Journal of the Endocrine Society. 1 (3): 186–201. doi:10.1210/js.2016-1048. PMC   5686660 . PMID   29264476.
  24. ↑ Sarathi V, Atluri S, Pradeep TV, Rallapalli SS, Rakesh CV, Sunanda T, Kumar KD (2019). "Utility of a Commercially Available Blood Steroid Profile in Endocrine Practice". Indian Journal of Endocrinology and Metabolism. 23 (1): 97–101. doi: 10.4103/ijem.IJEM_531_18 . PMC   6446682 . PMID   31016162.


This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.