11β-Hydroxyprogesterone

December 2023 vanc property raw P117 skin-invert-image 220px qualifier raw P117 P2096 11β-Hydroxypregn-4-ene-3,20-dione (1S,3aS,3bS,9aR,9bS,10S,11aS)-1-Acetyl-10-hydroxy-9a,11a-dimethyl-1,2,3,3a,3b,4,5,8,9,9a,9b,10,11,11a-tetradecahydro-7H-cyclopenta[a]phenanthren-7-one 11β-OHP; 21-Deoxycorticosterone; 21-Desoxycorticosterone 600-57-7 28247 2440888 91968 1S/C21H30O3/c1-12(22)16-6-7-17-15-5-4-13-10-14(23)8-9-20(13,2)19(15)18(24)11-21(16,17)3/h10,15-19,24H,4-9,11H2,1-3H3/t15-,16+,17-,18-,19+,20-,21+/m0/s1 BFZHCUBIASXHPK-ATWVFEABSA-N C05498 101788 CC(=O)[C@H]1CC[C@@H]2[C@@]1(C[C@@H]([C@H]3[C@H]2CCC4=CC(=O)CC[C@]34C)O)C 21 30 3 330.468 g/mol 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.http://www.hmdb.ca/metabolites/HMDB04031 hmdb.ca Human Metabolome Database: Showing metabocard for 11b-Hydroxyprogesterone (HMDB04031) 16 December 2016 21 December 2016 https://web.archive.org/web/20161221001304/http://www.hmdb.ca/metabolites/HMDB04031 live It is a potent mineralocorticoid. Syntheses of 11β-OHP from progesterone is catalyzed by the steroid 11β-hydroxylase (CYP11B1) enzyme, Strushkevich N, Gilep AA, Shen L, Arrowsmith CH, Edwards AM, Usanov SA, Park HW Structural insights into aldosterone synthase substrate specificity and targeted inhibition Molecular Endocrinology 27 2 315–24 February 2013 23322723 5417327 10.1210/me.2012-1287 van Rooyen D, Gent R, Barnard L, Swart AC The in vitro metabolism of 11β-hydroxyprogesterone and 11-ketoprogesterone to 11-ketodihydrotestosterone in the backdoor pathway The Journal of Steroid Biochemistry and Molecular Biology 178 203–212 April 2018 29277707 10.1016/j.jsbmb.2017.12.014 3700135 and, to a lesser extent, by the aldosterone synthase enzyme (CYP11B2). Function Along with its epimer 11α-hydroxyprogesterone (11α-OHP), 11β-OHP has been identified as a very potent competitive inhibitor of both isoforms (1 and 2) of 11β-hydroxysteroid dehydrogenase (11β-HSD). Souness GW, Latif SA, Laurenzo JL, Morris DJ 11 alpha- and 11 beta-hydroxyprogesterone, potent inhibitors of 11 beta-hydroxysteroid dehydrogenase (isoforms 1 and 2), confer marked mineralocorticoid activity on corticosterone in the ADX rat Endocrinology 136 4 1809–12 April 1995 7895695 10.1210/endo.136.4.7895695 Souness GW, Morris DJ 11 alpha- and 11 beta-hydroxyprogesterone, potent inhibitors of 11 beta-hydroxysteroid dehydrogenase, possess hypertensinogenic activity in the rat Hypertension 27 3 Pt 1 421–5 March 1996 8698448 10.1161/01.hyp.27.3.421 Outcome of 21-hydroxylase deficiency The steroid 11β-OHP has been known since 1987 to occur at increased levels in 21-hydroxylase deficiency. Gueux B, Fiet J, Galons H, Boneté R, Villette JM, Vexiau P, Pham-Huu-Trung MT, Raux-Eurin MC, Gourmelen M, Brérault JL 6 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 January 1987 3546944 10.1016/0022-4731(87)90043-4 primary Fiet J, Gueux B, Raux-DeMay MC, Kuttenn F, Vexiau P, Brerault JL, Couillin P, Galons H, Villette JM, Julien R 6 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 March 1989 2537337 10.1210/jcem-68-3-542 primary A study in 2017 has shown that in subjects with 21-hydroxylase deficiency, serum 11β-OHP concentrations range from 0.012 to 3.37 ng/mL, while in control group it was below detection limit of 0.012 ng/mL. Fiet J, Le Bouc Y, Guéchot J, Hélin N, Maubert MA, Farabos D, Lamazière A 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 March 2017 29264476 5686660 10.1210/js.2016-1048 primary 21-hydroxylase is an enzyme that is also involved in progesterone metabolism, producing 11-deoxycorticosterone. In normal conditions, 21-hydroxylase has higher activity on progesterone than steroid 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) that convert progesterone to 11β-OHP.November 2020 That's why in 21-hydroxylase deficiency, given the normal function of the CYP11B enzymes, the progesterone is directed towards 11β-OHP pathway rather than towards 11-deoxycorticosterone pathway, that is also usually accompanied by an increase in progesterone levels. Nie M, Cui MX, Mao JF, Tong AL, Chen S, Wang X, Lu L, Wu XY 6 [Possibility of progesterone as the diagnostic biomarker of 21-hydroxylase deficiency] Zhonghua Yi Xue Za Zhi 96 48 3866–3869 December 2016 28057154 10.3760/cma.j.issn.0376-2491.2016.48.003 In the normal route to aldosterone and cortisol, progesterone and 17α-hydroxyprogesterone are first hydroxylated at position 21 and then hydroxylated at other positions. In 21-hydroxylase deficiency, progesterone and 17α-hydroxyprogesterone accumulate and are the substrates of steroid 11β-hydroxylase, leading to 1β-OHP and 21-deoxycortisol, respectively. Turcu AF, Auchus RJ Adrenal steroidogenesis and congenital adrenal hyperplasia Endocrinology and Metabolism Clinics of North America 44 2 275–96 June 2015 26038201 4506691 10.1016/j.ecl.2015.02.002 In the 2017 study mentioned above, serum progesterone concentrations in boys (10 days to 18 years old) with 21-hydroxylase deficiency reached levels similar to female luteal values (up to 10.14 ng/mL, depending on severity and treatment), while in the control group of boys progesterone was 0.07 ng/mL (0.22 nmol/L) on average, ranged from 0.05 to 0.40 ng/mL. In a 2016 study, classical CAH patients receiving glucocorticoid therapy had C19 11-oxygenated steroid serum levels that were elevated 3-4 fold compared to healthy controls.Turcu AF, Nanba AT, Chomic R, Upadhyay SK, Giordano TJ, Shields JJ, Merke DP, Rainey WE, Auchus RJ 2016 Adrenal-derived 11-oxygenated 19-carbon steroids are the dominant androgens in classic 21-hydroxylase deficiency Eur J Endocrinol 174 5 601–9 10.1530/EJE-15-1181 4874183 26865584 In that same study, the levels of C19 11-oxygenated androgens correlated positively with conventional androgens in women but negatively in men. The levels of 11KT were four times higher than that of T in women with the condition. In adult women with CAH, the ratio of DHT produced in a backdoor pathway to that produced in a conventional pathway increases as control of androgen excess by glucocorticoid therapy deteriorates.Abiraterone acetate to lower androgens in women with classic 21-hydroxylase deficiency J Clin Endocrinol Metab 99 8 2763–70 2014 24780050 4121028 10.1210/jc.2014-1258 Auchus RJ, Buschur EO, Chang AY, Hammer GD, Ramm C, Madrigal D, Wang G, Gonzalez M, Xu XS, Smit JW, Jiao J, Yu MK In CAH patients with poor disease control, 11-oxygenated androgens remain elevated for longer than 17OHP, thus serving as a better biomarker for the effectiveness of the disease control.2021 24-Hour Profiles of 11-Oxygenated C19 Steroids and Δ5-Steroid Sulfates during Oral and Continuous Subcutaneous Glucocorticoids in 21-Hydroxylase Deficiency Front Endocrinol (Lausanne) 12 751191 10.3389/fendo.2021.751191 8636728 34867794 free Turcu AF, Mallappa A, Nella AA, Chen X, Zhao L, Nanba AT, Byrd JB, Auchus RJ, Merke DP11-Oxygenated Androgens Are Biomarkers of Adrenal Volume and Testicular Adrenal Rest Tumors in 21-Hydroxylase Deficiency The Journal of Clinical Endocrinology and Metabolism 102 8 2701–2710 10.1210/jc.2016-3989 5546849 28472487 Turcu AF, Mallappa A, Elman MS, Avila NA, Marko J, Rao H, Tsodikov A, Auchus RJ, Merke DP 2017 In males with CAH, 11-oxygenated androgen levels may indicate the presence testicular adrenal rest tumors.((Schröder MAM)), Turcu AF, O'Day P, van Herwaarden AE, Span PN, Auchus RJ, Sweep FC, Claahsen-van der Grinten HL 2022 Production of 11-Oxygenated Androgens by Testicular Adrenal Rest Tumors J Clin Endocrinol Metab 107 1 e272–e280 10.1210/clinem/dgab598 8684463 3439033710.15347/WJM/2023.003 free Alternative androgen pathways 2023 Masiutin M, Yadav M WikiJournal of Medicine 10 29 257943362 https://upload.wikimedia.org/wikiversity/en/a/a7/Alternative_androgens_pathways.pdfby4 yes While studies suggest that 11β-OHP, also known as 21-deoxycorticosterone, can be used as marker for adrenal 21-hydroxylase deficiency, another 21-carbon steroid — 21-deoxycortisol (produced from 17α-hydroxyprogesterone) gained acceptance for this purpose.Greaves RF, Kumar M, Mawad N, Francescon A, Le C, O'Connell M, Chi J, Pitt J 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 October 2023 58 37873849 10594498 10.3390/ijns9040058 free Cristoni S, Cuccato D, Sciannamblo M, Bernardi LR, Biunno I, Gerthoux P, Russo G, Weber G, Mora S 6 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 Communications in Mass Spectrometry 18 1 77–82 2004 14689562 10.1002/rcm.1284 2004RCMS...18...77C primary Sarathi V, Atluri S, Pradeep TV, Rallapalli SS, Rakesh CV, Sunanda T, Kumar KD Utility of a Commercially Available Blood Steroid Profile in Endocrine Practice Indian Journal of Endocrinology and Metabolism 23 1 97–101 2019 31016162 6446682 10.4103/ijem.IJEM_531_18 primary free See also 21-Deoxycortisol (11β,17α-dihydroxyprogesterone) 11-Deoxycorticosterone (21-hydroxyprogesterone) Corticosterone (11β,21-dihydroxyprogesterone) Cortisol (11β,17α,21-trihydroxyprogesterone) 11-Deoxycortisol (17α,21-dihydroxyprogesterone) 9α-Bromo-11-ketoprogesterone References 30em External links Metabocard for 11β-Hydroxyprogesterone (HMDB04031) - Human Metabolome Database Category:11β-Hydroxysteroid dehydrogenase inhibitors Category:Cyclohexanols Category:Diketones Category:Human metabolites Category:Mineralocorticoids Category:Pregnanes Category:Enones