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Wikipedia

5α-Pregnan-17α-ol-3,20-dione

April 12, 2024

5α-Pregnan-17α-ol-3,20-dione, also known as 17α-hydroxy-dihydroprogesterone (17‐OH-DHP) is an endogenous steroid, a metabolite of 17α-hydroxyprogesterone.

5α-Pregnan-17α-ol-3,20-dione
Names
IUPAC name
17α-Hydroxy-5α-pregnane-3,20-dione[5][6]
Systematic IUPAC name
(1R,3aS,3bR,5aS,9aS,9bS,11aS)-1-Acetyl-1-hydroxy-9a,11a-dimethylhexadecahydro-7H-cyclopenta[a]phenanthren-7-one
Other names
5α-17-Hydroxypregnane-3,20-dione,[1] 17‐OH-DHP,[2] 5α-Pregnane-17α-ol-3,20-dione,[2] 17-Hydroxydihydroprogesterone,[3] 17α-hydroxy-dihydroprogesterone[4]
Identifiers
  • 570-59-2
3D model (JSmol)
  • Interactive image
ChEMBL
  • ChEMBL1078989
ChemSpider
  • 10063888
  • 11889565
  • DTXSID30474538
  • Key: UUOHXXXJRQGPLC-JJFNZWTKSA-N
  • InChI=1S/C21H32O3/c1-13(22)21(24)11-8-18-16-5-4-14-12-15(23)6-9-19(14,2)17(16)7-10-20(18,21)3/h14,16-18,24H,4-12H2,1-3H3/t14-,16+,17-,18-,19-,20-,21-/m0/s1
  • CC(=O)[C@]1(CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CC[C@@H]4[C@@]3(CCC(=O)C4)C)C)O
Properties
C21H32O3
Molar mass 332.484 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Function edit

 
The androgen backdoor pathway (red arrows) roundabout testosterone embedded in within conventional androgen synthesis that lead to 5α-dihydrotestosterone through testosterone.[7][8][9]

5α-Pregnan-17α-ol-3,20-dione (17‐OH-DHP) is a progestogen, i.e., it binds to the progesterone receptors. However, 17‐OH-DHP is better studied as a metabolic intermediate than a progestogen per se.

17‐OH-DHP is the first intermediate product within the androgen backdoor pathway[7] in which 17α-hydroxyprogesterone (17‐OHP) is 5α-reduced and finally converted to 5α-dihydrotestosterone (DHT) without testosterone intermediate. The subsequent intermediate products in the pathway are 5α-pregnane-3α,17α-diol-20-one, androsterone and 5α-androstane-3α,17β-diol.[9][10] The primary feature of the androgen backdoor pathway is that 17α-hydroxyprogesterone (17-OHP) can be 5α-reduced and finally converted to 5α-dihydrotestosterone (DHT) via an alternative route that bypasses the conventional[11] intermediates androstenedione and testosterone.[12][13]

Biosynthesis edit

5α-Pregnan-17α-ol-3,20-dione is produced by 5α-reduction of 17-OHP. The reaction is catalyzed by SRD5A1[14] and possibly, SRD5A2 enzymes.[7] While the role of the SRD5A1 enzyme in this reaction is well established, it is unclear whether SRD5A2 is also involved.[13] Some authors[2][14] claim that the reduction of 17-OHP to 17OHDHP by SRD5A1 is not "sufficient" or "efficient", as supported by measurements of rat SRD5A2 activity in a 1971 study.[15] In a later study, conducted in 2017, however, it has been shown that recombinant human SRD5A1 and SRD5A2 can catalyze the reduction of 17-OHP at comparable rates to the reduction of progesterone.[16] Given both isozymes may be expressed in fetal tissues of both sexes,[17][18] the action of SRD5A2 in this reaction in humans is yet to be established.[7]

See also edit

References edit

  1. ^ "(5alpha)-17-Hydroxypregnane-3,20-dione - PubChem Compound Summary". from the original on 23 October 2020. Retrieved 21 October 2020.
  2. ^ a b c Fukami M, Homma K, Hasegawa T, Ogata T (April 2013). "Backdoor pathway for dihydrotestosterone biosynthesis: implications for normal and abnormal human sex development". Developmental Dynamics. 242 (4): 320–329. doi:10.1002/dvdy.23892. PMID 23073980. S2CID 44702659.
  3. ^ Miller WL (January 2012). "The syndrome of 17,20 lyase deficiency". The Journal of Clinical Endocrinology and Metabolism. 97 (1): 59–67. doi:10.1210/jc.2011-2161. PMC 3251937. PMID 22072737.
  4. ^ Hastings C, Hansson V (August 1981). "Kinetic properties of the soluble 3 alpha-hydroxysteroid dehydrogenase from rat testis and epididymis". Journal of Steroid Biochemistry. 14 (8): 705–711. doi:10.1016/0022-4731(81)90005-4. PMID 6946263.
  5. ^ Asahina K, Suzuki K, Aida K, Hibiya T, Tamaoki B (February 1985). "Relationship between the structures and steroidogenic functions of the testes of the urohaze-goby (Glossogobius olivaceus)". General and Comparative Endocrinology. 57 (2): 281–292. doi:10.1016/0016-6480(85)90273-4. PMID 3156787.
  6. ^ Gal M, Orly J (2014). "Selective inhibition of steroidogenic enzymes by ketoconazole in rat ovary cells". Clinical Medicine Insights. Reproductive Health. 8: 15–22. doi:10.4137/CMRH.S14036. PMC 4007567. PMID 24812532.
  7. ^ a b c d Masiutin MM, Yadav MK (3 April 2023). "Alternative androgen pathways" (PDF). WikiJournal of Medicine. 10: 29. doi:10.15347/WJM/2023.003. S2CID 257943362.  This article incorporates text from this source, which is available under the CC BY 4.0 license.
  8. ^ O'Shaughnessy PJ, Antignac JP, Le Bizec B, Morvan ML, Svechnikov K, Söder O, et al. (February 2019). Rawlins E (ed.). "Alternative (backdoor) androgen production and masculinization in the human fetus". PLOS Biology. 17 (2): e3000002. doi:10.1371/journal.pbio.3000002. PMC 6375548. PMID 30763313.
  9. ^ a b Miller WL, Auchus RJ (April 2019). "The "backdoor pathway" of androgen synthesis in human male sexual development". PLOS Biology. 17 (4): e3000198. doi:10.1371/journal.pbio.3000198. PMC 6464227. PMID 30943210.
  10. ^ Wilson JD, Auchus RJ, Leihy MW, Guryev OL, Estabrook RW, Osborn SM, et al. (February 2003). "5alpha-androstane-3alpha,17beta-diol is formed in tammar wallaby pouch young testes by a pathway involving 5alpha-pregnane-3alpha,17alpha-diol-20-one as a key intermediate". Endocrinology. 144 (2): 575–580. doi:10.1210/en.2002-220721. PMID 12538619.
  11. ^ Kinter KJ, Anekar AA (2021). Biochemistry, Dihydrotestosterone. StatPearls. PMID 32491566. from the original on 21 April 2023. Retrieved 16 July 2023.
  12. ^ Auchus RJ (November 2004). "The backdoor pathway to dihydrotestosterone". Trends in Endocrinology and Metabolism. 15 (9): 432–438. doi:10.1016/j.tem.2004.09.004. PMID 15519890. S2CID 10631647.
  13. ^ a b Kamrath C, Hochberg Z, Hartmann MF, Remer T, Wudy SA (March 2012). "Increased activation of the alternative "backdoor" pathway in patients with 21-hydroxylase deficiency: evidence from urinary steroid hormone analysis". The Journal of Clinical Endocrinology and Metabolism. 97 (3): E367–E375. doi:10.1210/jc.2011-1997. PMID 22170725. S2CID 3162065.
  14. ^ a b Reisch N, Taylor AE, Nogueira EF, Asby DJ, Dhir V, Berry A, et al. (October 2019). "Alternative pathway androgen biosynthesis and human fetal female virilization". Proceedings of the National Academy of Sciences of the United States of America. 116 (44): 22294–22299. Bibcode:2019PNAS..11622294R. doi:10.1073/pnas.1906623116. PMC 6825302. PMID 31611378.
  15. ^ Frederiksen DW, Wilson JD (April 1971). "Partial characterization of the nuclear reduced nicotinamide adenine dinucleotide phosphate: delta 4-3-ketosteroid 5 alpha-oxidoreductase of rat prostate". The Journal of Biological Chemistry. 246 (8): 2584–2593. doi:10.1016/S0021-9258(18)62328-2. PMID 4396507.
  16. ^ Barnard L, Gent R, van Rooyen D, Swart AC (November 2017). "Adrenal C11-oxy C21 steroids contribute to the C11-oxy C19 steroid pool via the backdoor pathway in the biosynthesis and metabolism of 21-deoxycortisol and 21-deoxycortisone". The Journal of Steroid Biochemistry and Molecular Biology. 174: 86–95. doi:10.1016/j.jsbmb.2017.07.034. PMID 28774496. S2CID 24071400.
  17. ^ Ellsworth K, Harris G (October 1995). "Expression of the type 1 and 2 steroid 5 alpha-reductases in human fetal tissues". Biochemical and Biophysical Research Communications. 215 (2): 774–780. doi:10.1006/bbrc.1995.2530. PMID 7488021.
  18. ^ Lunacek A, Schwentner C, Oswald J, Fritsch H, Sergi C, Thomas LN, et al. (August 2007). "Fetal distribution of 5alpha-reductase 1 and 5alpha-reductase 2, and their input on human prostate development". The Journal of Urology. 178 (2): 716–721. doi:10.1016/j.juro.2007.03.089. PMID 17574609.


 

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April 12, 2024
pregnan, 17α, dione, also, known, 17α, hydroxy, dihydroprogesterone, endogenous, steroid, metabolite, 17α, hydroxyprogesterone, namesiupac, name, 17α, hydroxy, pregnane, dione, systematic, iupac, name, 11as, acetyl, hydroxy, dimethylhexadecahydro, cyclopenta, . 5a Pregnan 17a ol 3 20 dione also known as 17a hydroxy dihydroprogesterone 17 OH DHP is an endogenous steroid a metabolite of 17a hydroxyprogesterone 5a Pregnan 17a ol 3 20 dione NamesIUPAC name 17a Hydroxy 5a pregnane 3 20 dione 5 6 Systematic IUPAC name 1R 3aS 3bR 5aS 9aS 9bS 11aS 1 Acetyl 1 hydroxy 9a 11a dimethylhexadecahydro 7H cyclopenta a phenanthren 7 oneOther names 5a 17 Hydroxypregnane 3 20 dione 1 17 OH DHP 2 5a Pregnane 17a ol 3 20 dione 2 17 Hydroxydihydroprogesterone 3 17a hydroxy dihydroprogesterone 4 IdentifiersCAS Number 570 59 23D model JSmol Interactive imageChEMBL ChEMBL1078989ChemSpider 10063888PubChem CID 11889565CompTox Dashboard EPA DTXSID30474538InChI Key UUOHXXXJRQGPLC JJFNZWTKSA NInChI 1S C21H32O3 c1 13 22 21 24 11 8 18 16 5 4 14 12 15 23 6 9 19 14 2 17 16 7 10 20 18 21 3 h14 16 18 24H 4 12H2 1 3H3 t14 16 17 18 19 20 21 m0 s1SMILES CC O C 1 CC C H 2 C 1 CC C H 3 C H 2CC C H 4 C 3 CCC O C4 C C OPropertiesChemical formula C 21H 32O 3Molar mass 332 484 g mol 1Except where otherwise noted data are given for materials in their standard state at 25 C 77 F 100 kPa Infobox referencesContents 1 Function 2 Biosynthesis 3 See also 4 ReferencesFunction edit nbsp The androgen backdoor pathway red arrows roundabout testosterone embedded in within conventional androgen synthesis that lead to 5a dihydrotestosterone through testosterone 7 8 9 5a Pregnan 17a ol 3 20 dione 17 OH DHP is a progestogen i e it binds to the progesterone receptors However 17 OH DHP is better studied as a metabolic intermediate than a progestogen per se 17 OH DHP is the first intermediate product within the androgen backdoor pathway 7 in which 17a hydroxyprogesterone 17 OHP is 5a reduced and finally converted to 5a dihydrotestosterone DHT without testosterone intermediate The subsequent intermediate products in the pathway are 5a pregnane 3a 17a diol 20 one androsterone and 5a androstane 3a 17b diol 9 10 The primary feature of the androgen backdoor pathway is that 17a hydroxyprogesterone 17 OHP can be 5a reduced and finally converted to 5a dihydrotestosterone DHT via an alternative route that bypasses the conventional 11 intermediates androstenedione and testosterone 12 13 Biosynthesis edit5a Pregnan 17a ol 3 20 dione is produced by 5a reduction of 17 OHP The reaction is catalyzed by SRD5A1 14 and possibly SRD5A2 enzymes 7 While the role of the SRD5A1 enzyme in this reaction is well established it is unclear whether SRD5A2 is also involved 13 Some authors 2 14 claim that the reduction of 17 OHP to 17OHDHP by SRD5A1 is not sufficient or efficient as supported by measurements of rat SRD5A2 activity in a 1971 study 15 In a later study conducted in 2017 however it has been shown that recombinant human SRD5A1 and SRD5A2 can catalyze the reduction of 17 OHP at comparable rates to the reduction of progesterone 16 Given both isozymes may be expressed in fetal tissues of both sexes 17 18 the action of SRD5A2 in this reaction in humans is yet to be established 7 See also editAndrogen backdoor pathway 5a DihydrotestosteroneReferences edit nbsp This article incorporates text available under the CC BY SA 3 0 license 5alpha 17 Hydroxypregnane 3 20 dione PubChem Compound Summary Archived from the original on 23 October 2020 Retrieved 21 October 2020 a b c Fukami M Homma K Hasegawa T Ogata T April 2013 Backdoor pathway for dihydrotestosterone biosynthesis implications for normal and abnormal human sex development Developmental Dynamics 242 4 320 329 doi 10 1002 dvdy 23892 PMID 23073980 S2CID 44702659 Miller WL January 2012 The syndrome of 17 20 lyase deficiency The Journal of Clinical Endocrinology and Metabolism 97 1 59 67 doi 10 1210 jc 2011 2161 PMC 3251937 PMID 22072737 Hastings C Hansson V August 1981 Kinetic properties of the soluble 3 alpha hydroxysteroid dehydrogenase from rat testis and epididymis Journal of Steroid Biochemistry 14 8 705 711 doi 10 1016 0022 4731 81 90005 4 PMID 6946263 Asahina K Suzuki K Aida K Hibiya T Tamaoki B February 1985 Relationship between the structures and steroidogenic functions of the testes of the urohaze goby Glossogobius olivaceus General and Comparative Endocrinology 57 2 281 292 doi 10 1016 0016 6480 85 90273 4 PMID 3156787 Gal M Orly J 2014 Selective inhibition of steroidogenic enzymes by ketoconazole in rat ovary cells Clinical Medicine Insights Reproductive Health 8 15 22 doi 10 4137 CMRH S14036 PMC 4007567 PMID 24812532 a b c d Masiutin MM Yadav MK 3 April 2023 Alternative androgen pathways PDF WikiJournal of Medicine 10 29 doi 10 15347 WJM 2023 003 S2CID 257943362 nbsp This article incorporates text from this source which is available under the CC BY 4 0 license O Shaughnessy PJ Antignac JP Le Bizec B Morvan ML Svechnikov K Soder O et al February 2019 Rawlins E ed Alternative backdoor androgen production and masculinization in the human fetus PLOS Biology 17 2 e3000002 doi 10 1371 journal pbio 3000002 PMC 6375548 PMID 30763313 a b Miller WL Auchus RJ April 2019 The backdoor pathway of androgen synthesis in human male sexual development PLOS Biology 17 4 e3000198 doi 10 1371 journal pbio 3000198 PMC 6464227 PMID 30943210 Wilson JD Auchus RJ Leihy MW Guryev OL Estabrook RW Osborn SM et al February 2003 5alpha androstane 3alpha 17beta diol is formed in tammar wallaby pouch young testes by a pathway involving 5alpha pregnane 3alpha 17alpha diol 20 one as a key intermediate Endocrinology 144 2 575 580 doi 10 1210 en 2002 220721 PMID 12538619 Kinter KJ Anekar AA 2021 Biochemistry Dihydrotestosterone StatPearls PMID 32491566 Archived from the original on 21 April 2023 Retrieved 16 July 2023 Auchus RJ November 2004 The backdoor pathway to dihydrotestosterone Trends in Endocrinology and Metabolism 15 9 432 438 doi 10 1016 j tem 2004 09 004 PMID 15519890 S2CID 10631647 a b Kamrath C Hochberg Z Hartmann MF Remer T Wudy SA March 2012 Increased activation of the alternative backdoor pathway in patients with 21 hydroxylase deficiency evidence from urinary steroid hormone analysis The Journal of Clinical Endocrinology and Metabolism 97 3 E367 E375 doi 10 1210 jc 2011 1997 PMID 22170725 S2CID 3162065 a b Reisch N Taylor AE Nogueira EF Asby DJ Dhir V Berry A et al October 2019 Alternative pathway androgen biosynthesis and human fetal female virilization Proceedings of the National Academy of Sciences of the United States of America 116 44 22294 22299 Bibcode 2019PNAS 11622294R doi 10 1073 pnas 1906623116 PMC 6825302 PMID 31611378 Frederiksen DW Wilson JD April 1971 Partial characterization of the nuclear reduced nicotinamide adenine dinucleotide phosphate delta 4 3 ketosteroid 5 alpha oxidoreductase of rat prostate The Journal of Biological Chemistry 246 8 2584 2593 doi 10 1016 S0021 9258 18 62328 2 PMID 4396507 Barnard L Gent R van Rooyen D Swart AC November 2017 Adrenal C11 oxy C21 steroids contribute to the C11 oxy C19 steroid pool via the backdoor pathway in the biosynthesis and metabolism of 21 deoxycortisol and 21 deoxycortisone The Journal of Steroid Biochemistry and Molecular Biology 174 86 95 doi 10 1016 j jsbmb 2017 07 034 PMID 28774496 S2CID 24071400 Ellsworth K Harris G October 1995 Expression of the type 1 and 2 steroid 5 alpha reductases in human fetal tissues Biochemical and Biophysical Research Communications 215 2 774 780 doi 10 1006 bbrc 1995 2530 PMID 7488021 Lunacek A Schwentner C Oswald J Fritsch H Sergi C Thomas LN et al August 2007 Fetal distribution of 5alpha reductase 1 and 5alpha reductase 2 and their input on human prostate development The Journal of Urology 178 2 716 721 doi 10 1016 j juro 2007 03 089 PMID 17574609 nbsp This article about a steroid is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title 5a Pregnan 17a ol 3 20 dione amp oldid 1218302141, wikipedia, wiki, book, books, library,

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