5α-Pregnane-3α,17α-diol-20-one

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5α-Pregnane-3α,17α-diol-20-one
5-alpha-Pregnane-3-alpha 17-alpha-diol-20-one.svg
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
PubChem CID
  • 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).
Comparison of chemical structures for allopregnane, allopregnanolone and 5a-Pregnane-3a,17a-diol-20-one (17a-allopregnanolone). Please note that the difference between the allopregnanolone and 5a-Pregnane-3a,17a-diol-20-one is a hydroxyl function group (-OH) at C17 position. 17-alpha-hydroxyallopregnanolone-comparison-3-pregnanes.svg
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.
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. Trimethyl steroid-nomenclature.svg
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.

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

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] [14] [20]

Biosynthesis

5α-Pregnane-3α,17α-diol-20-one is produced from 5α-pregnan-17α-ol-3,20-dione [21] in a reaction catalyzed by a reductive 3α-hydroxysteroid dehydrogenase (3α-HSD), [22] i.e. by the two aldo-keto reductase isozymes: AKR1C2 and AKR1C4, [23] and by 17β-hydroxysteroid dehydrogenase 6 (HSD17B6) that also has the 3α-HSD activity. [23]

See also

Related Research Articles

<span class="mw-page-title-main">Steroid</span> Polycyclic organic compound having sterane as a core structure

A steroid is an organic compound with four fused rings arranged in a specific molecular configuration.

<span class="mw-page-title-main">Androsterone</span> Endogenous steroid hormone

Androsterone, or 3α-hydroxy-5α-androstan-17-one, is an endogenous steroid hormone, neurosteroid, and putative pheromone. It is a weak androgen with a potency that is approximately 1/7 that of testosterone. Androsterone is a metabolite of testosterone and dihydrotestosterone (DHT). In addition, it can be converted back into DHT via 3α-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase, bypassing conventional intermediates such as androstanedione and testosterone, and as such, can be considered to be a metabolic intermediate in its own right.

<span class="mw-page-title-main">Dihydrotestosterone</span> Human hormone

Dihydrotestosterone is an endogenous androgen sex steroid and hormone primarily involved in the growth and repair of the prostate and the penis, as well as the production of sebum and body hair composition.

<span class="mw-page-title-main">5α-Reductase</span> Enzyme family

5α-Reductases, also known as 3-oxo-5α-steroid 4-dehydrogenases, are enzymes involved in steroid metabolism. They participate in three metabolic pathways: bile acid biosynthesis, androgen and estrogen metabolism. There are three isozymes of 5α-reductase encoded by the genes SRD5A1, SRD5A2, and SRD5A3.

<span class="mw-page-title-main">Allopregnanolone</span> Endogenous inhibitory neurosteroid

Allopregnanolone is a naturally occurring neurosteroid which is made in the body from the hormone progesterone. As a medication, allopregnanolone is referred to as brexanolone, sold under the brand name Zulresso, and used to treat postpartum depression. It is given by injection into a vein.

<span class="mw-page-title-main">SRD5A1</span> Protein-coding gene in the species Homo sapiens

3-Oxo-5α-steroid 4-dehydrogenase 1 is an enzyme that in humans is encoded by the SRD5A1 gene. It is one of three forms of steroid 5α-reductase.

<span class="mw-page-title-main">3α-Androstanediol</span> Chemical compound

3α-Androstanediol also known as 5α-androstane-3α,17β-diol and sometimes shortened in the literature to 3α-diol, is an endogenous steroid hormone and neurosteroid and a metabolite of androgens like dihydrotestosterone (DHT).

<span class="mw-page-title-main">5α-Dihydroprogesterone</span> Chemical compound

5α-Dihydroprogesterone is an endogenous progestogen and neurosteroid that is synthesized from progesterone. It is also an intermediate in the synthesis of allopregnanolone and isopregnanolone from progesterone.

<span class="mw-page-title-main">3β-Androstanediol</span> Chemical compound

3β-Androstanediol, also known as 5α-androstane-3β,17β-diol, and sometimes shortened in the literature to 3β-diol, is an endogenous steroid hormone and a metabolite of androgens like dehydroepiandrosterone (DHEA) and dihydrotestosterone (DHT).

<span class="mw-page-title-main">5β-Dihydroprogesterone</span> Chemical compound

5β-Dihydroprogesterone is an endogenous neurosteroid and an intermediate in the biosynthesis of pregnanolone and epipregnanolone from progesterone. It is synthesized from progesterone by the enzyme 5β-reductase.

<span class="mw-page-title-main">Allopregnanediol</span> Chemical compound

Allopregnanediol, or 5α-pregnane-3α,20α-diol, is an endogenous metabolite of progesterone and allopregnanolone and an isomer of pregnanediol (5β-pregnan-3α,20α-diol). It has been found to act like a partial agonist of an allosteric site of the GABA receptor and hence might play a biological role as a neurosteroid. It has also been found to act as an agonist of the human pregnane X receptor, albeit with an EC50 that is more than an order of magnitude lower than that of other endogenous pregnanes like pregnenolone, pregnanediol, allopregnanedione, and allopregnanolone.

Pregnanolone, also known as tetrahydroprogesterone (THP), may refer to:

<span class="mw-page-title-main">11β-Hydroxyprogesterone</span> Chemical compound

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. It is a potent mineralocorticoid. Syntheses of 11β-OHP from progesterone is catalyzed by the steroid 11β-hydroxylase (CYP11B1) enzyme, and, to a lesser extent, by the aldosterone synthase enzyme (CYP11B2).

<span class="mw-page-title-main">5α-Dihydroethisterone</span> Chemical compound

5α-Dihydroethisterone is an active metabolite of the formerly clinically used but now-discontinued progestin ethisterone and the experimental and never-marketed hormonal antineoplastic agent ethynylandrostanediol (HE-3235). Its formation from its parent drugs is catalyzed by 5α-reductase in tissues that express the enzyme in high amounts like the liver, skin, hair follicles, and prostate gland. 5α-DHET has significant affinity for steroid hormone receptors and may contribute importantly to the activities of its parent drugs.

<span class="mw-page-title-main">Androgen backdoor pathway</span> Series of interconnected biochemical reactions

The androgen backdoor pathway synthesizes physiologically relevant androgens from 21-carbon steroids (pregnanes) via 5α-reduction, bypassing testosterone. This differs from the conventional, canonical androgenic pathway, which involves testosterone.

<span class="mw-page-title-main">5α-Pregnan-17α-ol-3,20-dione</span> Chemical compound

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.

<span class="mw-page-title-main">11-Ketoandrosterone</span> Chemical compound

11-Ketoandrosterone is an endogenous steroid.

<span class="mw-page-title-main">5α-Pregnane-3α,11β-diol-20-one</span> Chemical compound

5α-Pregnane-3α,11β-diol-20-one, abbreviated as 3,11diOH-DHP4, also known as 3α,11β-dihydroxy-5α-pregnan-20-one, is an endogenous steroid.

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. ↑ Bremer AA, Miller WL (2014). "Regulation of Steroidogenesis". Cellular Endocrinology in Health and Disease. Academic Press. 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. 1 2 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. 1 2 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. 1 2 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. ↑ 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.
  21. ↑ 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.
  22. ↑ 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)
  23. 1 2 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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