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3β-Androstanediol

February 15, 2024

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).

3β-Androstanediol
Names
IUPAC name
5α-Androstane-3β,17β-diol
Systematic IUPAC name
(1S,3aS,3bR,5aS,7S,9aS,9bS,11aS)-9a,11a-Dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-1,7-diol
Other names
3β-Androstanediol; 3β-Diol; Maxterone
Identifiers
  • 571-20-0 Y
3D model (JSmol)
  • Interactive image
ChEMBL
  • ChEMBL316048
ChemSpider
  • 211834
ECHA InfoCard 100.008.487
  • 242332
UNII
  • 6J0K4253QD Y
  • DTXSID8022379
  • InChI=1S/C19H32O2/c1-18-9-7-13(20)11-12(18)3-4-14-15-5-6-17(21)19(15,2)10-8-16(14)18/h12-17,20-21H,3-11H2,1-2H3/t12-,13-,14-,15-,16-,17-,18-,19-/m0/s1
    Key: CBMYJHIOYJEBSB-YSZCXEEOSA-N
  • InChI=1/C19H32O2/c1-18-9-7-13(20)11-12(18)3-4-14-15-5-6-17(21)19(15,2)10-8-16(14)18/h12-17,20-21H,3-11H2,1-2H3/t12-,13-,14-,15-,16-,17-,18-,19-/m0/s1
    Key: CBMYJHIOYJEBSB-YSZCXEEOBK
  • O[C@H]4CC[C@]3([C@@H](CC[C@H]2[C@@H]1CC[C@H](O)[C@@]1(C)CC[C@@H]23)C4)C
Properties
C19H32O2
Molar mass 292.463 g·mol−1
Melting point 168–170 °C (334–338 °F; 441–443 K)[1]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Biological activity edit

3β-Androstanediol is a selective, high-affinity agonist of the ERβ, and hence, an estrogen.[2] In contrast to ERβ, 3β-androstanediol does not bind to the androgen receptor (AR).[3] 3β-Androstanediol has been reported to also bind to ERα with low nanomolar affinity, with several-fold lower affinity relative to ERβ.[4][5] It has approximately 3% and 7% of the affinity of estradiol at the ERα and ERβ, respectively.[6] Unlike 3α-androstanediol, 3β-androstanediol does not bind to the GABAA receptor.[7]

3β-Androstanediol may be the primary endogenous ligand of ERβ in the prostate gland, and as a result of activation of the ERβ, 3β-androstanediol has antiproliferative effects against prostate cancer cells.[8] Through the ERβ, 3β-androstanediol positively regulates oxytocin neurons and signaling in the paraventricular nucleus of hypothalamus,[9][10] and has been found to have antidepressant,[11] anxiolytic,[12] cognitive-enhancing,[12] and stress-relieving effects via this action.[13][14] Androgens, including testosterone and DHT, are known to downregulate the hypothalamic-pituitary-adrenal axis, and this has been found to be due in part or full to their conversion into 3β-androstanediol rather than to activation of the AR.[13][14][15]

Biochemistry edit

Testosterone metabolism in humans
 
 
This diagram illustrates the metabolic pathways involved in the metabolism of DHT in humans. In addition to the transformations shown in the diagram, conjugation (e.g., sulfation and glucuronidation) occurs with DHT and metabolites that have one or more available hydroxyl (–OH) groups.

3β-Androstanediol is a 5α-reduced and 17β-hydroxylated metabolite of dehydroepiandrosterone (DHEA) as well as a 3β-hydroxylated metabolite of DHT (and by extension of testosterone).

A determination of the circulating levels of 3β-androstanediol in humans found concentrations of 239 ± 76 pg/ml and 82 ± 45 pg/ml of the compound in normal male and female serum, respectively.[16]

3β-Androstanediol shows high affinity for sex hormone-binding globulin (SHBG), similar to that of DHT.[17]

Chemistry edit

3β-Androstanediol, also known as 5α-androstane-3β,17β-diol, is a naturally occurring androstane steroid and a structural analogue of DHT (5α-androstan-17β-ol-3-one). A notable epimer of 3β-androstanediol is 3α-androstanediol.

17α-Ethynyl-3β-androstanediol is a 17α-substituted derivative of 3β-androstanediol and is an estrogen similarly.[18][19]

References edit

  1. ^ Wang, Xingbin; Liu, Hui; Yan, Peiyun; Liu, Jinliang; Li, Yan; Sun, Qian; Wang, Cunde (1 May 2011). "Simultaneously rapid deprotection of 3-acyloxy groups and reduction of D-ring ketones (nitrile) of steroids using DIBAL-H/NiCl2". Journal of Chemical Research. 35 (5): 291–293. doi:10.3184/174751911X13050949941793. S2CID 197144530.
  2. ^ C.Y. Cheng (24 October 2009). Molecular Mechanisms in Spermatogenesis. Springer Science & Business Media. pp. 259–. ISBN 978-0-387-09597-4.
  3. ^ Oliveira AG, Coelho PH, Guedes FD, Mahecha GA, Hess RA, Oliveira CA (December 2007). "5alpha-Androstane-3beta,17beta-diol (3beta-diol), an estrogenic metabolite of 5alpha-dihydrotestosterone, is a potent modulator of estrogen receptor ERbeta expression in the ventral prostrate of adult rats". Steroids. 72 (14): 914–22. doi:10.1016/j.steroids.2007.08.001. PMID 17854852. S2CID 54258086.
  4. ^ Baker ME (2002). "Recent insights into the origins of adrenal and sex steroid receptors" (PDF). J. Mol. Endocrinol. 28 (3): 149–52. doi:10.1677/jme.0.0280149. PMID 12063181.
  5. ^ Kuiper, George G. J. M.; Carlsson, Bo; Grandien, Kaj; Enmark, Eva; Häggblad, Johan; Nilsson, Stefan; Gustafsson, Jan-Åke (1997). "Comparison of the Ligand Binding Specificity and Transcript Tissue Distribution of Estrogen Receptors α and β". Endocrinology. 138 (3): 863–870. doi:10.1210/endo.138.3.4979. ISSN 0013-7227. PMID 9048584.
  6. ^ Kuiper GG, Carlsson B, Grandien K, Enmark E, Häggblad J, Nilsson S, Gustafsson JA (1997). "Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta". Endocrinology. 138 (3): 863–70. doi:10.1210/endo.138.3.4979. PMID 9048584.
  7. ^ Reddy, D. S.; Jian, K. (2010). "The Testosterone-Derived Neurosteroid Androstanediol Is a Positive Allosteric Modulator of GABAA Receptors". Journal of Pharmacology and Experimental Therapeutics. 334 (3): 1031–1041. doi:10.1124/jpet.110.169854. ISSN 0022-3565. PMC 2939675. PMID 20551294.
  8. ^ Weihua Z, Lathe R, Warner M, Gustafsson JA (October 2002). "An endocrine pathway in the prostate, ERbeta, AR, 5alpha-androstane-3beta,17beta-diol, and CYP7B1, regulates prostate growth". Proceedings of the National Academy of Sciences of the United States of America. 99 (21): 13589–94. Bibcode:2002PNAS...9913589W. doi:10.1073/pnas.162477299. PMC 129718. PMID 12370428.
  9. ^ Sharma, Dharmendra; Handa, Robert J.; Uht, Rosalie M. (2012). "The ERβ Ligand 5α-androstane, 3β,17β-diol (3β-diol) Regulates Hypothalamic Oxytocin (Oxt) Gene Expression". Endocrinology. 153 (5): 2353–2361. doi:10.1210/en.2011-1002. ISSN 0013-7227. PMC 3339641. PMID 22434086.
  10. ^ Hiroi, Ryoko; Lacagnina, Anthony F.; Hinds, Laura R.; Carbone, David G.; Uht, Rosalie M.; Handa, Robert J. (2013). "The Androgen Metabolite, 5α-Androstane-3β,17β-Diol (3β-Diol), Activates the Oxytocin Promoter Through an Estrogen Receptor-β Pathway". Endocrinology. 154 (5): 1802–1812. doi:10.1210/en.2012-2253. ISSN 0013-7227. PMC 3628024. PMID 23515287.
  11. ^ Huang, Q; Zhu, H; Fischer, D; Zhou, J (2008). "An estrogenic effect of 5α-androstane-3β, 17β-diol on the behavioral response to stress and on CRH regulation". Neuropharmacology. 54 (8): 1233–1238. doi:10.1016/j.neuropharm.2008.03.016. ISSN 0028-3908. PMID 18457850. S2CID 9052079.
  12. ^ a b Frye, C; Koonce, C; Edinger, K; Osborne, D; Walf, A (2008). "Androgens with activity at estrogen receptor beta have anxiolytic and cognitive-enhancing effects in male rats and mice". Hormones and Behavior. 54 (5): 726–734. doi:10.1016/j.yhbeh.2008.07.013. ISSN 0018-506X. PMC 3623974. PMID 18775724.
  13. ^ a b Handa, R. J.; Weiser, M. J.; Zuloaga, D. G. (2009). "A Role for the Androgen Metabolite, 5α-Androstane-3β,17β-Diol, in Modulating Oestrogen Receptor β-Mediated Regulation of Hormonal Stress Reactivity". Journal of Neuroendocrinology. 21 (4): 351–358. doi:10.1111/j.1365-2826.2009.01840.x. ISSN 0953-8194. PMC 2727750. PMID 19207807.
  14. ^ a b Handa, Robert J.; Sharma, Dharmendra; Uht, Rosalie (2011). "A Role for the Androgen Metabolite, 5alpha Androstane 3beta, 17beta Diol (3?-Diol) in the Regulation of the Hypothalamo-Pituitary?Adrenal Axis". Frontiers in Endocrinology. 2: 65. doi:10.3389/fendo.2011.00065. ISSN 1664-2392. PMC 3355903. PMID 22649380.
  15. ^ Handa, Robert J.; Pak, Toni R.; Kudwa, Andrea E.; Lund, Trent D.; Hinds, Laura (2008). "An alternate pathway for androgen regulation of brain function: Activation of estrogen receptor beta by the metabolite of dihydrotestosterone, 5α-androstane-3β,17β-diol". Hormones and Behavior. 53 (5): 741–752. doi:10.1016/j.yhbeh.2007.09.012. ISSN 0018-506X. PMC 2430080. PMID 18067894.
  16. ^ Laband P, Tresguerres JA, Lisboa BP, Volkwein U, Tamm J (August 1978). "The determination of 5alpha-androstane-3alpha, 17beta-diol in human plasma by radioimmunoassay". Acta Endocrinologica. 88 (4): 778–86. doi:10.1530/acta.0.0880778. PMID 581118.
  17. ^ Hong H, Branham WS, Ng HW, Moland CL, Dial SL, Fang H, Perkins R, Sheehan D, Tong W (February 2015). "Human sex hormone-binding globulin binding affinities of 125 structurally diverse chemicals and comparison with their binding to androgen receptor, estrogen receptor, and α-fetoprotein". Toxicol. Sci. 143 (2): 333–48. doi:10.1093/toxsci/kfu231. PMID 25349334.
  18. ^ Beyler AL, Clinton RO (June 1956). "Uterine growth stimulating and testicular growth suppressing activities of 17alpha-ethinylandrostane-3beta, 17beta-diol, its delta 5-analog and derivatives". Proc. Soc. Exp. Biol. Med. 92 (2): 404–8. doi:10.3181/00379727-92-22493. PMID 13350363. S2CID 87469965.
  19. ^ Ahlem C, Kennedy M, Page T, Bell D, Delorme E, Villegas S, Reading C, White S, Stickney D, Frincke J (February 2012). "17α-alkynyl 3α, 17β-androstanediol non-clinical and clinical pharmacology, pharmacokinetics and metabolism". Invest New Drugs. 30 (1): 59–78. doi:10.1007/s10637-010-9517-0. PMID 20814732. S2CID 24785562.


February 15, 2024
androstanediol, also, known, androstane, 17β, diol, sometimes, shortened, literature, diol, endogenous, steroid, hormone, metabolite, androgens, like, dehydroepiandrosterone, dhea, dihydrotestosterone, namesiupac, name, androstane, 17β, diolsystematic, iupac, . 3b Androstanediol also known as 5a androstane 3b 17b diol and sometimes shortened in the literature to 3b diol is an endogenous steroid hormone and a metabolite of androgens like dehydroepiandrosterone DHEA and dihydrotestosterone DHT 3b Androstanediol NamesIUPAC name 5a Androstane 3b 17b diolSystematic IUPAC name 1S 3aS 3bR 5aS 7S 9aS 9bS 11aS 9a 11a Dimethylhexadecahydro 1H cyclopenta a phenanthrene 1 7 diolOther names 3b Androstanediol 3b Diol MaxteroneIdentifiersCAS Number 571 20 0 Y3D model JSmol Interactive imageChEMBL ChEMBL316048ChemSpider 211834ECHA InfoCard 100 008 487PubChem CID 242332UNII 6J0K4253QD YCompTox Dashboard EPA DTXSID8022379InChI InChI 1S C19H32O2 c1 18 9 7 13 20 11 12 18 3 4 14 15 5 6 17 21 19 15 2 10 8 16 14 18 h12 17 20 21H 3 11H2 1 2H3 t12 13 14 15 16 17 18 19 m0 s1Key CBMYJHIOYJEBSB YSZCXEEOSA NInChI 1 C19H32O2 c1 18 9 7 13 20 11 12 18 3 4 14 15 5 6 17 21 19 15 2 10 8 16 14 18 h12 17 20 21H 3 11H2 1 2H3 t12 13 14 15 16 17 18 19 m0 s1Key CBMYJHIOYJEBSB YSZCXEEOBKSMILES O C H 4CC C 3 C H CC C H 2 C H 1CC C H O C 1 C CC C H 23 C4 CPropertiesChemical formula C 19H 32O 2Molar mass 292 463 g mol 1Melting point 168 170 C 334 338 F 441 443 K 1 Except where otherwise noted data are given for materials in their standard state at 25 C 77 F 100 kPa Infobox references Contents 1 Biological activity 2 Biochemistry 3 Chemistry 4 ReferencesBiological activity edit3b Androstanediol is a selective high affinity agonist of the ERb and hence an estrogen 2 In contrast to ERb 3b androstanediol does not bind to the androgen receptor AR 3 3b Androstanediol has been reported to also bind to ERa with low nanomolar affinity with several fold lower affinity relative to ERb 4 5 It has approximately 3 and 7 of the affinity of estradiol at the ERa and ERb respectively 6 Unlike 3a androstanediol 3b androstanediol does not bind to the GABAA receptor 7 3b Androstanediol may be the primary endogenous ligand of ERb in the prostate gland and as a result of activation of the ERb 3b androstanediol has antiproliferative effects against prostate cancer cells 8 Through the ERb 3b androstanediol positively regulates oxytocin neurons and signaling in the paraventricular nucleus of hypothalamus 9 10 and has been found to have antidepressant 11 anxiolytic 12 cognitive enhancing 12 and stress relieving effects via this action 13 14 Androgens including testosterone and DHT are known to downregulate the hypothalamic pituitary adrenal axis and this has been found to be due in part or full to their conversion into 3b androstanediol rather than to activation of the AR 13 14 15 Biochemistry editvte Testosterone metabolism in humans nbsp nbsp This diagram illustrates the metabolic pathways involved in the metabolism of DHT in humans In addition to the transformations shown in the diagram conjugation e g sulfation and glucuronidation occurs with DHT and metabolites that have one or more available hydroxyl OH groups 3b Androstanediol is a 5a reduced and 17b hydroxylated metabolite of dehydroepiandrosterone DHEA as well as a 3b hydroxylated metabolite of DHT and by extension of testosterone A determination of the circulating levels of 3b androstanediol in humans found concentrations of 239 76 pg ml and 82 45 pg ml of the compound in normal male and female serum respectively 16 3b Androstanediol shows high affinity for sex hormone binding globulin SHBG similar to that of DHT 17 Chemistry edit3b Androstanediol also known as 5a androstane 3b 17b diol is a naturally occurring androstane steroid and a structural analogue of DHT 5a androstan 17b ol 3 one A notable epimer of 3b androstanediol is 3a androstanediol 17a Ethynyl 3b androstanediol is a 17a substituted derivative of 3b androstanediol and is an estrogen similarly 18 19 References edit Wang Xingbin Liu Hui Yan Peiyun Liu Jinliang Li Yan Sun Qian Wang Cunde 1 May 2011 Simultaneously rapid deprotection of 3 acyloxy groups and reduction of D ring ketones nitrile of steroids using DIBAL H NiCl2 Journal of Chemical Research 35 5 291 293 doi 10 3184 174751911X13050949941793 S2CID 197144530 C Y Cheng 24 October 2009 Molecular Mechanisms in Spermatogenesis Springer Science amp Business Media pp 259 ISBN 978 0 387 09597 4 Oliveira AG Coelho PH Guedes FD Mahecha GA Hess RA Oliveira CA December 2007 5alpha Androstane 3beta 17beta diol 3beta diol an estrogenic metabolite of 5alpha dihydrotestosterone is a potent modulator of estrogen receptor ERbeta expression in the ventral prostrate of adult rats Steroids 72 14 914 22 doi 10 1016 j steroids 2007 08 001 PMID 17854852 S2CID 54258086 Baker ME 2002 Recent insights into the origins of adrenal and sex steroid receptors PDF J Mol Endocrinol 28 3 149 52 doi 10 1677 jme 0 0280149 PMID 12063181 Kuiper George G J M Carlsson Bo Grandien Kaj Enmark Eva Haggblad Johan Nilsson Stefan Gustafsson Jan Ake 1997 Comparison of the Ligand Binding Specificity and Transcript Tissue Distribution of Estrogen Receptors a and b Endocrinology 138 3 863 870 doi 10 1210 endo 138 3 4979 ISSN 0013 7227 PMID 9048584 Kuiper GG Carlsson B Grandien K Enmark E Haggblad J Nilsson S Gustafsson JA 1997 Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta Endocrinology 138 3 863 70 doi 10 1210 endo 138 3 4979 PMID 9048584 Reddy D S Jian K 2010 The Testosterone Derived Neurosteroid Androstanediol Is a Positive Allosteric Modulator of GABAA Receptors Journal of Pharmacology and Experimental Therapeutics 334 3 1031 1041 doi 10 1124 jpet 110 169854 ISSN 0022 3565 PMC 2939675 PMID 20551294 Weihua Z Lathe R Warner M Gustafsson JA October 2002 An endocrine pathway in the prostate ERbeta AR 5alpha androstane 3beta 17beta diol and CYP7B1 regulates prostate growth Proceedings of the National Academy of Sciences of the United States of America 99 21 13589 94 Bibcode 2002PNAS 9913589W doi 10 1073 pnas 162477299 PMC 129718 PMID 12370428 Sharma Dharmendra Handa Robert J Uht Rosalie M 2012 The ERb Ligand 5a androstane 3b 17b diol 3b diol Regulates Hypothalamic Oxytocin Oxt Gene Expression Endocrinology 153 5 2353 2361 doi 10 1210 en 2011 1002 ISSN 0013 7227 PMC 3339641 PMID 22434086 Hiroi Ryoko Lacagnina Anthony F Hinds Laura R Carbone David G Uht Rosalie M Handa Robert J 2013 The Androgen Metabolite 5a Androstane 3b 17b Diol 3b Diol Activates the Oxytocin Promoter Through an Estrogen Receptor b Pathway Endocrinology 154 5 1802 1812 doi 10 1210 en 2012 2253 ISSN 0013 7227 PMC 3628024 PMID 23515287 Huang Q Zhu H Fischer D Zhou J 2008 An estrogenic effect of 5a androstane 3b 17b diol on the behavioral response to stress and on CRH regulation Neuropharmacology 54 8 1233 1238 doi 10 1016 j neuropharm 2008 03 016 ISSN 0028 3908 PMID 18457850 S2CID 9052079 a b Frye C Koonce C Edinger K Osborne D Walf A 2008 Androgens with activity at estrogen receptor beta have anxiolytic and cognitive enhancing effects in male rats and mice Hormones and Behavior 54 5 726 734 doi 10 1016 j yhbeh 2008 07 013 ISSN 0018 506X PMC 3623974 PMID 18775724 a b Handa R J Weiser M J Zuloaga D G 2009 A Role for the Androgen Metabolite 5a Androstane 3b 17b Diol in Modulating Oestrogen Receptor b Mediated Regulation of Hormonal Stress Reactivity Journal of Neuroendocrinology 21 4 351 358 doi 10 1111 j 1365 2826 2009 01840 x ISSN 0953 8194 PMC 2727750 PMID 19207807 a b Handa Robert J Sharma Dharmendra Uht Rosalie 2011 A Role for the Androgen Metabolite 5alpha Androstane 3beta 17beta Diol 3 Diol in the Regulation of the Hypothalamo Pituitary Adrenal Axis Frontiers in Endocrinology 2 65 doi 10 3389 fendo 2011 00065 ISSN 1664 2392 PMC 3355903 PMID 22649380 Handa Robert J Pak Toni R Kudwa Andrea E Lund Trent D Hinds Laura 2008 An alternate pathway for androgen regulation of brain function Activation of estrogen receptor beta by the metabolite of dihydrotestosterone 5a androstane 3b 17b diol Hormones and Behavior 53 5 741 752 doi 10 1016 j yhbeh 2007 09 012 ISSN 0018 506X PMC 2430080 PMID 18067894 Laband P Tresguerres JA Lisboa BP Volkwein U Tamm J August 1978 The determination of 5alpha androstane 3alpha 17beta diol in human plasma by radioimmunoassay Acta Endocrinologica 88 4 778 86 doi 10 1530 acta 0 0880778 PMID 581118 Hong H Branham WS Ng HW Moland CL Dial SL Fang H Perkins R Sheehan D Tong W February 2015 Human sex hormone binding globulin binding affinities of 125 structurally diverse chemicals and comparison with their binding to androgen receptor estrogen receptor and a fetoprotein Toxicol Sci 143 2 333 48 doi 10 1093 toxsci kfu231 PMID 25349334 Beyler AL Clinton RO June 1956 Uterine growth stimulating and testicular growth suppressing activities of 17alpha ethinylandrostane 3beta 17beta diol its delta 5 analog and derivatives Proc Soc Exp Biol Med 92 2 404 8 doi 10 3181 00379727 92 22493 PMID 13350363 S2CID 87469965 Ahlem C Kennedy M Page T Bell D Delorme E Villegas S Reading C White S Stickney D Frincke J February 2012 17a alkynyl 3a 17b androstanediol non clinical and clinical pharmacology pharmacokinetics and metabolism Invest New Drugs 30 1 59 78 doi 10 1007 s10637 010 9517 0 PMID 20814732 S2CID 24785562 Retrieved from https en wikipedia org w index php title 3b Androstanediol amp oldid 1188194088, wikipedia, wiki, book, books, library,

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