5α-Pregnane-3α,17α-diol-20-one

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

5α-Pregnane-3α,17α-diol-20-one
Names
IUPAC name
3α,17-Dihydroxy-5α-pregnan-20-one[1]
Systematic IUPAC name
1-[(1R,3aS,3bR,5aS,7R,9aS,9bS,11aS)-1,7-Dihydroxy-9a,11a-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-1-yl]ethan-1-one
Other names
5α-pregnan-3α,17α-diol-20-one,[2][3][4] 5α-pregnane-3α,17α-diol-20-one,[5][6] 3α,5α-3,17-dihydroxypregnan-20-one,[7] 17-hydroxyallopregnanolone,[8][9][10][11][12][13] 17‐OH-allopregnanolone.[14][15][4][16]
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
EC Number
  • 229-994-6
  • Key: LKQDFQLSEHWIRK-JRRMKBMNSA-N
  • InChI=1S/C21H34O3/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/h14-18,23-24H,4-12H2,1-3H3/t14-,15+,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(CC[C@H](C4)O)C)C)O
Properties
C21H34O3
Molar mass 334.500 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references
Comparison of chemical structures for allopregnane, allopregnanolone and 5α-Pregnane-3α,17α-diol-20-one (17α-allopregnanolone). Please note that the difference between the allopregnanolone and 5α-Pregnane-3α,17α-diol-20-one is a hydroxyl function group (−OH) at C17 position.
Complex chemical diagram
Structure of cholestane, a steroid with 27 carbon atoms. Its core ring system (ABCD), composed of 17 carbon atoms, is shown with IUPAC-approved ring lettering and atom numbering.

Function

5α-Pregnane-3α,17α-diol-20-one is a metabolite, an intermediate product within the androgen backdoor pathway[17] in which 17α-hydroxyprogesterone (17‐OHP) is 5α-reduced and finally converted to 5α-dihydrotestosterone (DHT) without testosterone as a metabolic intermediate.[18][6]

The pathway can be outlined as 17-OHP → 5α-pregnan-17α-ol-3,20-dione → 5α-pregnane-3α,17α-diol-20-one → androsterone → 5α-androstane-3α,17β-diol → DHT.[19][20][21]

Biosynthesis

5α-Pregnane-3α,17α-diol-20-one is produced from 5α-pregnan-17α-ol-3,20-dione[22] in a reaction catalyzed by a reductive 3α-hydroxysteroid dehydrogenase (3α-HSD),[23] i.e. by the two aldo-keto reductase isozymes: AKR1C2 and AKR1C4,[24] and by 17β-hydroxysteroid dehydrogenase 6 (HSD17B6) that also has the 3α-HSD activity.[24]

See also

References
  1. "3α,17-dihydroxy-5α-pregnan-20-one substance infocard".
  2. 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.
  3. Andrew A. Bremer; Walter L. Miller (2014). "Regulation of Steroidogenesis". Cellular Endocrinology in Health and Disease. pp. 207–227. doi:10.1016/B978-0-12-408134-5.00013-5. ISBN 978-0-12-408134-5. Most steroids are identified by their common names; 17-hydroxy-dihydroprogesterone (17OH-DHP) is 5α-pregnane-17α-ol-3,20-dione; 17-hydroxy-allopregnanolone (17OH-allo) is 5α-pregnan-3α,17α-diol-20-one; 5α-dihydroprogesterone (5α-DHP) is 5α-pregnane-3,20-dione, and allopregnanolone is 3α-hydroxy-dihydroprogesterone (3α-OH-DHP) or 5α-pregnane-3α-ol-20-one.
  4. Gupta MK, Guryev OL, Auchus RJ (October 2003). "5alpha-reduced C21 steroids are substrates for human cytochrome P450c17". Archives of Biochemistry and Biophysics. 418 (2): 151–160. doi:10.1016/j.abb.2003.07.003. PMID 14522586.
  5. 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.
  6. 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.
  7. "ChemSpider Chemical Structure: 99828".
  8. Cytochrome P450: Structure, Mechanism, and Biochemistry. Springer. 13 March 2015. ISBN 9783319121086. 17-OH-Allo 5α-pregnane-3α,17α-diol-20-one (17-hydroxyallopregnanolone)
  9. Sanders E, Slenter D, Willighagen E, Hemel I, Bot WM, Ehrhart F, et al. (23 June 2021). "The alternative pathway of fetal androgen synthesis (Homo sapiens)". 17-Hydroxyallopregnanolone, Metabolite, CHEBI:11909 (ChEBI)
  10. Reisch N, Idkowiak J, Hughes BA, Ivison HE, Abdul-Rahman OA, Hendon LG, et al. (March 2013). "Prenatal diagnosis of congenital adrenal hyperplasia caused by P450 oxidoreductase deficiency". The Journal of Clinical Endocrinology and Metabolism. 98 (3): E528–E536. doi:10.1210/jc.2012-3449. PMC 3708032. PMID 23365120. 17-hydroxyallopregnanolone (5-pregnane-3,17-diol-20-one)
  11. Prasad VV, Mathur C, Welch M, Lieberman S (May 1992). "Steroidogenic potential of lyophilized mitochondria from bovine adrenocortical tissue". Proceedings of the National Academy of Sciences of the United States of America. 89 (9): 4173–4177. Bibcode:1992PNAS...89.4173P. doi:10.1073/pnas.89.9.4173. PMC 525655. PMID 1570344.
  12. Honců P, Hill M, Bičíková M, Jandová D, Velíková M, Kajzar J, et al. (July 2019). "Activation of Adrenal Steroidogenesis and an Improvement of Mood Balance in Postmenopausal Females after Spa Treatment Based on Physical Activity". International Journal of Molecular Sciences. 20 (15): 3687. doi:10.3390/ijms20153687. PMC 6695846. PMID 31357645.
  13. Reisch N, Dhir V, Berry A, Taylor A, Krone N, Nogueira E, Shackleton C, Hanley N, Arlt W (April 2011). "Evidence for the existence and significance of an alternative pathway towards androgen synthesis during early human life". Endocrine Abstracts. 25.
  14. 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.
  15. Mostaghel EA (2014). "Beyond T and DHT - novel steroid derivatives capable of wild type androgen receptor activation". International Journal of Biological Sciences. 10 (6): 602–613. doi:10.7150/ijbs.8844. PMC 4062953. PMID 24948873.
  16. Saito K, Matsuzaki T, Iwasa T, Miyado M, Saito H, Hasegawa T, et al. (April 2016). "Steroidogenic pathways involved in androgen biosynthesis in eumenorrheic women and patients with polycystic ovary syndrome". The Journal of Steroid Biochemistry and Molecular Biology. 158: 31–37. doi:10.1016/j.jsbmb.2016.02.010. PMID 26877255. S2CID 22243788.
  17. Masiutin M, Yadav M (2023). "Alternative androgen pathways". WikiJournal of Medicine. 10: X. doi:10.15347/WJM/2023.003. S2CID 257943362.
  18. 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.
  19. O'Shaughnessy PJ, Antignac JP, Le Bizec B, Morvan ML, Svechnikov K, Söder O, et al. (February 2019). "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.
  20. 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.
  21. 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.
  22. Baronio F, Ortolano R, Menabò S, Cassio A, Baldazzi L, Di Natale V, et al. (September 2019). "46,XX DSD due to Androgen Excess in Monogenic Disorders of Steroidogenesis: Genetic, Biochemical, and Clinical Features". International Journal of Molecular Sciences. 20 (18): 4605. doi:10.3390/ijms20184605. PMC 6769793. PMID 31533357.
  23. Sharifi N, McPhaul MJ, Auchus RJ (December 2010). ""Getting from here to there"--mechanisms and limitations to the activation of the androgen receptor in castration-resistant prostate cancer". Journal of Investigative Medicine. 58 (8): 938–944. doi:10.2310/JIM.0b013e3181ff6bb8. PMC 5589138. PMID 21030877. The product of 17-hydroxyprogesterone reduction, 5α-pregnan-17α-ol-3,20-dione, was metabolized by a reductive 3α-HSD to a new key intermediate, 5α-pregnane-3α,17α-diol-20-one (Pdiol)
  24. 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.
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