Chemistry:5α-Pregnan-17α-ol-3,20-dione

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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
3D model (JSmol)
ChEMBL
ChemSpider
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).
Infobox references

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.

Function

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

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

References

  1. ↑ "(5alpha)-17-Hydroxypregnane-3,20-dione - PubChem Compound Summary". https://pubchem.ncbi.nlm.nih.gov/compound/11889565. 
  2. ↑ 2.0 2.1 2.2 "Backdoor pathway for dihydrotestosterone biosynthesis: implications for normal and abnormal human sex development". Developmental Dynamics 242 (4): 320–329. April 2013. doi:10.1002/dvdy.23892. PMID 23073980. 
  3. ↑ "The syndrome of 17,20 lyase deficiency". The Journal of Clinical Endocrinology and Metabolism 97 (1): 59–67. January 2012. doi:10.1210/jc.2011-2161. PMID 22072737. 
  4. ↑ "Kinetic properties of the soluble 3 alpha-hydroxysteroid dehydrogenase from rat testis and epididymis". Journal of Steroid Biochemistry 14 (8): 705–711. August 1981. doi:10.1016/0022-4731(81)90005-4. PMID 6946263. 
  5. ↑ "Relationship between the structures and steroidogenic functions of the testes of the urohaze-goby (Glossogobius olivaceus)". General and Comparative Endocrinology 57 (2): 281–292. February 1985. doi:10.1016/0016-6480(85)90273-4. PMID 3156787. 
  6. ↑ "Selective inhibition of steroidogenic enzymes by ketoconazole in rat ovary cells". Clinical Medicine Insights. Reproductive Health 8: 15–22. 2014. doi:10.4137/CMRH.S14036. PMID 24812532. 
  7. ↑ 7.0 7.1 7.2 7.3 "Alternative androgen pathways". WikiJournal of Medicine 10: X. 2023. doi:10.15347/WJM/2023.003. 
  8. ↑ "Alternative (backdoor) androgen production and masculinization in the human fetus". PLOS Biology 17 (2): e3000002. February 2019. doi:10.1371/journal.pbio.3000002. PMID 30763313. 
  9. ↑ 9.0 9.1 "The "backdoor pathway" of androgen synthesis in human male sexual development". PLOS Biology 17 (4): e3000198. April 2019. doi:10.1371/journal.pbio.3000198. PMID 30943210. 
  10. ↑ "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. February 2003. doi:10.1210/en.2002-220721. PMID 12538619. 
  11. ↑ Biochemistry, Dihydrotestosterone. StatPearls. 2021. https://www.ncbi.nlm.nih.gov/books/NBK557634/. 
  12. ↑ "The backdoor pathway to dihydrotestosterone". Trends in Endocrinology and Metabolism 15 (9): 432–438. November 2004. doi:10.1016/j.tem.2004.09.004. PMID 15519890. 
  13. ↑ 13.0 13.1 "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. March 2012. doi:10.1210/jc.2011-1997. PMID 22170725. 
  14. ↑ 14.0 14.1 "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. October 2019. doi:10.1073/pnas.1906623116. PMID 31611378. Bibcode: 2019PNAS..11622294R. 
  15. ↑ "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. April 1971. doi:10.1016/S0021-9258(18)62328-2. PMID 4396507. 
  16. ↑ "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. November 2017. doi:10.1016/j.jsbmb.2017.07.034. PMID 28774496. 
  17. ↑ "Expression of the type 1 and 2 steroid 5 alpha-reductases in human fetal tissues". Biochemical and Biophysical Research Communications 215 (2): 774–780. October 1995. doi:10.1006/bbrc.1995.2530. PMID 7488021. 
  18. ↑ "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. August 2007. doi:10.1016/j.juro.2007.03.089. PMID 17574609. 




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