11-Deoxycortisol

December 2023 vanc February 2024 changed changed 390185893 property raw P117 skin-invert-image 220px Cortodoxone chemical structure property raw P8224 bg-transparent 220px Cortodoxone 3D ball molecule view 17α,21-Dihydroxypregn-4-ene-3,20-dione (1R,3aS,3bR,9aR,9bS,11aS)-1-Hydroxy-1-(2-hydroxy-1-oxoethyl)-9a,11a-dimethyl-1,2,3,3a,3b,4,5,8,9,9a,9b,10,11,11a-tetradecahydro-7H-cyclopenta[a]phenanthren-7-one 11-Deoxycortisol; 11-Deoxycortisone; Cortoxelone; 17α,21-Dihydroxyprogesterone; 11-Desoxycortisol; 11-Deoxyhydrocortisone; 11-Desoxyhydrocortisone; 17α-Hydroxy-11-deoxycorticosterone; Reichstein's Substance S; Compound S; Cortodoxone; Cortexolone, 5100 correct chemspider 389582 correct FDA WDT5SLP0HQ 1/C21H30O4/c1-19-8-5-14(23)11-13(19)3-4-15-16(19)6-9-20(2)17(15)7-10-21(20,25)18(24)12-22/h11,15-17,22,25H,3-10,12H2,1-2H3/t15-,16+,17+,19+,20+,21+/m1/s1 WHBHBVVOGNECLV-OBQKJFGGBG changed chemspider 1S/C21H30O4/c1-19-8-5-14(23)11-13(19)3-4-15-16(19)6-9-20(2)17(15)7-10-21(20,25)18(24)12-22/h11,15-17,22,25H,3-10,12H2,1-2H3/t15-,16+,17+,19+,20+,21+/m1/s1 changed chemspider WHBHBVVOGNECLV-OBQKJFGGSA-N correct CAS 152-58-9 440707 changed kegg D03595 changed EBI 28324 O=C4\C=C2/[C@]([C@H]1CC[C@@]3([C@@](O)(C(=O)CO)CC[C@H]3[C@@H]1CC2)C)(C)CC4 changed EBI 253144 21 30 4 215 11-Deoxycortisol, also known as cortodoxone (INN), cortexolone Rosette C, Agan FJ, Rosette N, Mazzetti A, Moro L, Gerloni M The dual androgen receptor and glucocorticoid receptor antagonist CB-03-10 as a potential treatment for tumors that have acquired GR-mediated resistance to AR blockade Molecular Cancer Therapeutics 2256–2266 August 2020 19 11 32847976 10.1158/1535-7163.MCT-19-1137 221345484 free https://figshare.com/articles/journal_contribution/22520836 Iaderets VV, Andriushina VA, Bartoshevich IE, Domracheva AG, Novak MI, Stytsenko TS, Voĭshvillo NE [A study of steroid hydroxylation activity of Curvularia lunata mycelium] ru Prikladnaia Biokhimiia I Mikrobiologiia 43 6 695–700 2007 18173113 Manosroi J, Chisti Y, Manosroi A Biotransformation of cortexolone to hydrocortisone by molds using a rapid color development assay Prikladnaia Biokhimiia I Mikrobiologiia 42 5 547–51 2006 17066954 Lisowska K, Długoński J Concurrent corticosteroid and phenanthrene transformation by filamentous fungus Cunninghamella elegans The Journal of Steroid Biochemistry and Molecular Biology 85 1 63–9 May 2003 12798358 10.1016/s0960-0760(03)00136-5 384672 as well as 17α,21-dihydroxyprogesterone or 17α,21-dihydroxypregn-4-ene-3,20-dione,R.A. Hill H.L.J. Makin D.N. Kirk G.M. Murphy Dictionary of Steroids https://books.google.com/books?id=qw5X0NK1A90C&pg=PA338 23 May 1991 CRC Press 978-0-412-27060-4 338– is an endogenous glucocorticoid steroid hormone, and a metabolic intermediate toward cortisol. The compound was first described by Tadeusz Reichstein in 1938 as Substance S,https://onlinelibrary.wiley.com/doi/10.1002/hlca.193802101183 10.1002/hlca.193802101183 Über Bestandteile der Nebennierenrinde. 21. Mitteilung. Die Konstitution der Substanzen R und S 1938 Helvetica Chimica Acta 21 1490–1497 Reichstein T 1938HChAc..21.1490R subscription 5 October 2020 10 October 2020 https://web.archive.org/web/20201010063404/https://onlinelibrary.wiley.com/doi/10.1002/hlca.193802101183 live thus has also been referred to as Reichstein's Substance S or Compound S. Wudy SA, Hartmann M, Homoki J Determination of 11-deoxycortisol (Reichstein's compound S) in human plasma by clinical isotope dilution mass spectrometry using benchtop gas chromatography-mass selective detection Steroids 67 10 851–7 September 2002 12231120 10.1016/s0039-128x(02)00052-1 29970823 Berneis K, Staub JJ, Gessler A, Meier C, Girard J, Müller B Combined stimulation of adrenocorticotropin and compound-S by single dose metyrapone test as an outpatient procedure to assess hypothalamic-pituitary-adrenal function The Journal of Clinical Endocrinology and Metabolism 87 12 5470–5 December 2002 12466339 10.1210/jc.2001-011959 free Function thumb|left|class=skin-invert-image|Steroidogenesis, showing 11-deoxycortisol in the pathway from cholesterol to cortisol.Häggström Mikael Richfield David 2014 Diagram of the pathways of human steroidogenesis WikiJournal of Medicine 1 1 10.15347/wjm/2014.005 2002-4436 free 11-Deoxycortisol acts as a glucocorticoid, though is less potent than cortisol. Engels M, Pijnenburg-Kleizen KJ, Utari A, Faradz SM, Oude-Alink S, van Herwaarden AE, Span PN, Sweep FC, Claahsen-van der Grinten HL Glucocorticoid Activity of Adrenal Steroid Precursors in Untreated Patients With Congenital Adrenal Hyperplasia The Journal of Clinical Endocrinology and Metabolism 104 11 5065–5072 November 2019 31090904 10.1210/jc.2019-00547 free 11-Deoxycortisol is synthesized from 17α-hydroxyprogesterone by 21-hydroxylase and is converted to cortisol by 11β-hydroxylase. 11-Deoxycortisol in mammals has limited biological activity and mainly acts as metabolic intermediate within the glucocorticoid pathway, leading to cortisol.Congenital Adrenal Hyperplasia Caused by 11Beta-Hydroxylase Deficiency Merck Manuals Professional Edition https://www.merckmanuals.com/professional/pediatrics/endocrine-disorders-in-children/congenital-adrenal-hyperplasia-caused-by-11beta-hydroxylase-deficiency 3 October 2020 25 September 2020 https://web.archive.org/web/20200925031158/https://www.merckmanuals.com/professional/pediatrics/endocrine-disorders-in-children/congenital-adrenal-hyperplasia-caused-by-11beta-hydroxylase-deficiency live However, in sea lampreys, an early jawless fish species that originated over 500 million years ago, 11-deoxycortisol is the primary and ultimate glucocorticoid hormone with mineralocorticoid properties; 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. Barany A, Shaughnessy CA, McCormick SD Corticosteroid control of Na+/K+-ATPase in the intestine of the sea lamprey (Petromyzon marinus) General and Comparative Endocrinology 307 113756 March 2021 33741310 10.1016/j.ygcen.2021.113756 2021GCEnd.30713756B 232296805 Sea lampreys do not possess the 11β-hydroxylase enzyme (CYP11B1) responsible for converting 11-deoxycortisol to cortisol and 11-deoxycorticosterone to corticosterone, as observed in mammals. The absence of this enzyme in sea lampreys indicates the existence of a complex and highly specific corticosteroid signaling pathway that emerged at least 500 million years ago with the advent of early vertebrates. The lack of cortisol and corticosterone in sea lampreys suggests that the presence of the 11β-hydroxylase enzyme may have been absent during the early stages of vertebrate evolution. Shaughnessy CA, Barany A, McCormick SD 11-Deoxycortisol controls hydromineral balance in the most basal osmoregulating vertebrate, sea lamprey (Petromyzon marinus) Scientific Reports 10 1 12148 July 2020 32699304 7376053 10.1038/s41598-020-69061-4 free 2020NatSR..1012148S The absence of cortisol and corticosterone in sea lampreys suggests that the 11β-hydroxylase enzyme may not have been present early in vertebrate evolution. Close DA, Yun SS, McCormick SD, Wildbill AJ, Li W 11-deoxycortisol is a corticosteroid hormone in the lamprey Proceedings of the National Academy of Sciences of the United States of America 107 31 13942–7 August 2010 20643930 2922276 10.1073/pnas.0914026107 2010PNAS..10713942C free left Clinical significance 11-Deoxycortisol in mammals has limited glucocorticoid activity, but it is the direct precursor of the major mammalian glucocorticoid, cortisol. Zöllner A, Kagawa N, Waterman MR, Nonaka Y, Takio K, Shiro Y, Hannemann F, Bernhardt R Purification and functional characterization of human 11beta hydroxylase expressed in Escherichia coli The FEBS Journal 275 4 799–810 February 2008 18215163 10.1111/j.1742-4658.2008.06253.x 45997341 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.https://www.healio.com/news/endocrinology/20190430/serum-steroid-levels-can-help-differentiate-adrenal-disorders Serum steroid levels can help differentiate adrenal disorders 3 October 2020 7 November 2020 https://web.archive.org/web/20201107051241/https://www.healio.com/news/endocrinology/20190430/serum-steroid-levels-can-help-differentiate-adrenal-disorders live In 11β-hydroxylase deficiency, 11-deoxycortisol and 11-deoxycorticosterone levels increase, and excess of 11-deoxycorticosterone leads to mineralocorticoid-based hypertension Gupta V Mineralocorticoid hypertension Indian Journal of Endocrinology and Metabolism 15 Suppl 4 October 2011 S298-312 22145132 3230101 10.4103/2230-8210.86972 free (as opposed to 21-hydroxylase deficiency, in which patients have low blood pressure from a lack of mineralocorticoids). Low levels of cortisol can affect blood pressure by causing a decrease in sodium retention and volume expansion. This effect occurs because cortisol regulates the balance of water and electrolytes in the body. When cortisol levels are low, there is less sodium reabsorption by the kidneys, leading to increased excretion of sodium through urine. This ultimately reduces blood volume and lowers blood pressure. On the other hand, high levels of cortisol can also affect blood pressure by causing an increase in sodium retention and volume expansion. Cortisol-induced hypertension is accompanied by significant sodium retention, leading to an increase in extracellular fluid volume and exchangeable sodium. This expansion results in an increase in blood volume and subsequently increases blood pressure. The underlying mechanisms for these effects involve various factors such as suppression of the nitric oxide system, alterations in vascular responsiveness to pressor agonists like adrenaline, increased cardiac output or stroke volume due to plasma volume expansion, and potential dysregulation of glucocorticoid receptors or 11β-hydroxylase enzyme activity. These mechanisms may be relevant to cortisol-induced hypertension and to conditions such as Cushing's syndrome (excess cortisol production), apparent mineralocorticoid excess (related to defects in 11β-hydroxylase enzymes), licorice abuse (glycyrrhetinic acid affecting glycyrrhetinic acid receptor),Li YL, Zhu XM, Liang H, Orvig C, Chen ZF Recent Advances in Asialoglycoprotein Receptor and Glycyrrhetinic Acid Receptor-Mediated and/or pH-Responsive Hepatocellular Carcinoma- Targeted Drug Delivery Curr Med Chem 28 8 1508–1534 2021 32368967 10.2174/0929867327666200505085756 chronic renal failure (prolonged half-life of cortisol due to reduced 11β-hydroxylase activity), and even essential hypertension where there may be abnormalities with 11β-hydroxylase activity or glucocorticoid receptor variations.Kelly JJ, Mangos G, Williamson PM, Whitworth JA Cortisol and hypertension Clin Exp Pharmacol Physiol Suppl 25 S51–6 November 1998 9809193 10.1111/j.1440-1681.1998.tb02301.x 13428727 van Uum SH, Lenders JW, Hermus AR Cortisol, 11beta-hydroxysteroid dehydrogenases, and hypertension Semin Vasc Med 4 2 121–8 May 2004 15478032 10.1055/s-2004-835369 260371999 Stewart PM Cortisol, hypertension and obesity: the role of 11 beta-hydroxysteroid dehydrogenase J R Coll Physicians Lond 32 2 154–9 1998 9597634 9663025 Low levels of cortisol lead to reduced vascular tone as cortisol helps maintain normal vascular tone by promoting vasoconstriction. Low levels of cortisol can lead to decreased vasoconstriction, resulting in relaxed blood vessels and lower overall blood pressure. Also, low cortisol levels lead to impaired fluid balance, as cortisol affects fluid balance by influencing sodium and water reabsorption in the kidneys. When cortisol levels are low, sodium absorption may be reduced, leading to increased excretion of sodium in the urine and subsequent lowering of blood volume and blood pressure. Additionally, low levels of cortisol cause a dysregulated renin-angiotensin system, as cortisol interacts with the renin-angiotensin system, which regulates blood pressure through vasoconstriction and fluid balance. Low cortisol levels can disrupt this system, leading to altered angiotensin production, reduced aldosterone secretion, and subsequently lower blood pressure. Conversely, high levels of cortisol lead to increased vascular tone, enhanced sodium retention, and increased sympathetic activity. Stress-induced release of high-level glucocorticoids such as cortisol activates the sympathetic nervous system (SNS). The SNS controls heart rate, cardiac output, and vasomotor tone, causing constriction, and thereby increasing peripheral arterial resistance, resulting in an increase in blood pressure.Lewandowski KC, Tadros-Zins M, Horzelski W, Krekora M, Lewinski A Renin, Aldosterone, and Cortisol in Pregnancy-Induced Hypertension Exp Clin Endocrinol Diabetes 131 4 222–227 April 2023 36807213 10101736 10.1055/a-2025-0510 In 11β-hydroxylase deficiency, 11-deoxycortisol can also be converted to androstenedione in a pathway that could explain the increase in androstenedione levels this condition.Auzéby A, Bogdan A, Touitou Y Evidence for a new biologic pathway of androstenedione synthesis from 11-deoxycortisol Steroids 56 1 33–6 January 1991 2028480 10.1016/0039-128X(91)90112-9 6261965 In 21-hydroxylase deficiency, 11-deoxycortisol levels are low.2013 Springer Science & Business Media Essential Endocrinology: A Primer for Nonspecialists 978-1-4899-1692-1 263 History In 1934, biochemist Tadeus Reichstein, working in Switzerland, began research on extracts from animal adrenal glands in order to isolate physiologically active compounds.https://www.nobelprize.org/prizes/medicine/1950/reichstein/lecture/ Chemistry of the Adrenal Cortex Hormones 5 October 2020 10 October 2020 https://web.archive.org/web/20201010072404/https://www.nobelprize.org/prizes/medicine/1950/reichstein/lecture/ live He was publishing results of his findings along the way. By 1944, he already isolated and explained the chemical structure of 29 pure substances. Grzybowski A, Pietrzak K Tadeusz Reichstein (1897-1996): a cofounder of modern steroid treatment in dermatology Clinics in Dermatology 30 2 243–7 2012 22435119 10.1016/j.clindermatol.2011.09.003 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 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. 13242571 Metabolism of 11-deoxycortisol in vitro The Journal of Biological Chemistry 215 2 713–22 1 August 1955 10.1016/S0021-9258(18)65996-4 free Forchielli E, Rosenkrantz H, Dorfman RI In 1949, American research chemist Percy Lavon Julian, in looking for ways to produce cortisone, announced the synthesis of the Compound S, from the cheap and readily available pregnenolone (synthesized from the soybean oil sterol stigmasterol).30 September 1949 Science gets synthetic key to rare drug; discovery is made in Chicago Chicago Tribune 1 https://pqasb.pqarchiver.com/chicagotribune/access/494372192.html?dids=494372192:494372192&FMT=ABS&FMTS=ABS:AI https://archive.today/20130131211933/http://pqasb.pqarchiver.com/chicagotribune/access/494372192.html?dids=494372192:494372192&FMT=ABS&FMTS=ABS:AI 31 January 2013 Dr. Julian's new method for synthesizing the anti-arthritis compound, cortisone, is less costly than present methods, because it eliminates the need for utilizing osmium tetroxide, a rare and expensive chemical, the Glidden company declared....But whether has Dr. Julian has also synthesized cortisone from soybeans neither he nor the Glidden company would reveal.10 October 1949 News of the week: New cortisone synthesis Chemical & Engineering News 27 41 2936–2942 Quote: A new synthesis of cortisone, eliminating the need for expensive osmium tetroxide, and the synthesis of three other compounds related to cortisone, which may possible be useful in the treatment of arthritis, have been announced by Percy L. Julian, director of research of the soya products division of the Glidden Co., Chicago. No statement was made as to further details of the new synthesis, but it was revealed that soybean products were not involved...all three [other compounds] were made from soybean sterols. 10.1021/cen-v027n041.p2936 On 5 April 1952, biochemist Durey Peterson and microbiologist Herbert Murray at Upjohn, published the first report of a breakthrough fermentation process for the microbial 11α-oxygenation of steroids (e.g. progesterone) in a single step by common molds of the order Mucorales.Peterson DH Murray, HC 1952 Microbiological oxygenation of steroids at carbon 11 J Am Chem Soc 74 7 1871–2 10.1021/ja01127a531 1952JAChS..74.1871P 11α-oxygenation of Compound S produces 11α-hydrocortisone, which can be chemically oxidized to cortisone, or converted by further chemical steps to 11β-hydrocortisone (cortisol). See also 11-Deoxycorticosterone Cortexolone 17α-propionate References Category:Corticosteroids Category:Glucocorticoids Category:Metabolic intermediates Category:Mineralocorticoids Category:Pregnanes Category:Steroid hormones Category:Steroids