3β-Androstanediolのソースを表示

{{Chembox
| ImageFile = 3beta-Androstanediol.svg
| ImageClass = skin-invert
| ImageSize = 250px
| IUPACName = 5α-Androstane-3β,17β-diol
| SystematicName = (1''S'',3a''S'',3b''R'',5a''S'',7''S'',9a''S'',9b''S'',11a''S'')-9a,11a-Dimethylhexadecahydro-1''H''-cyclopenta[''a'']phenanthrene-1,7-diol
| OtherNames = 3β-Androstanediol; 3β-Diol; Maxterone
|Section1={{Chembox Identifiers
| CASNo = 571-20-0
| CASNo_Ref = {{cascite|correct|CAS}}
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 6J0K4253QD
| PubChem = 242332
| ChemSpiderID = 211834
| ChEMBL = 316048
| SMILES = 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
| 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
| InChIKey = CBMYJHIOYJEBSB-YSZCXEEOBK
| StdInChI = 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
| StdInChIKey = CBMYJHIOYJEBSB-YSZCXEEOSA-N
  }}
|Section2={{Chembox Properties
| C=19 | H=32 | O=2
| Appearance = 
| Density = 
| MeltingPtC = 168-170 
| MeltingPt_ref =<ref>{{cite journal|last1=Wang|first1=Xingbin|last2=Liu|first2=Hui|last3=Yan|first3=Peiyun|last4=Liu|first4=Jinliang|last5=Li|first5=Yan|last6=Sun|first6=Qian|last7=Wang|first7=Cunde|title=Simultaneously rapid deprotection of 3-acyloxy groups and reduction of D-ring ketones (nitrile) of steroids using DIBAL-H/NiCl<SUB>2</SUB>|journal=Journal of Chemical Research|date=1 May 2011|volume=35|issue=5|pages=291–293|doi=10.3184/174751911X13050949941793|s2cid=197144530}}</ref>
| BoilingPt = 
| Solubility =
  }}
|Section3={{Chembox Hazards
| MainHazards = 
| FlashPt = 
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  }}
}}

'''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 [[androgen]]s like [[dehydroepiandrosterone]] (DHEA) and [[dihydrotestosterone]] (DHT).

==Biological activity==
3β-Androstanediol is a selective, high-[[affinity (pharmacology)|affinity]] [[agonist]] of the [[Estrogen receptor beta|ERβ]], and hence, an [[estrogen]].<ref name="Cheng2009">{{cite book|author =C.Y. Cheng|title=Molecular Mechanisms in Spermatogenesis|url=https://books.google.com/books?id=tdpVNN80_r0C&pg=PA259|date=24 October 2009|publisher=Springer Science & Business Media|isbn=978-0-387-09597-4|pages=259–}}</ref> In contrast to ERβ, 3β-androstanediol does not bind to the [[androgen receptor]] (AR).<ref name="pmid17854852">{{cite journal | vauthors = Oliveira AG, Coelho PH, Guedes FD, Mahecha GA, Hess RA, Oliveira CA | title = 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 | journal = Steroids | volume = 72 | issue = 14 | pages = 914–22 |date=December 2007 | pmid = 17854852 | doi = 10.1016/j.steroids.2007.08.001 | s2cid = 54258086 }}</ref> 3β-Androstanediol has been reported to also bind to [[ERα]] with low [[nanomolar]] affinity, with several-fold lower affinity relative to ERβ.<ref name="pmid12063181">{{cite journal | vauthors = Baker ME | title = Recent insights into the origins of adrenal and sex steroid receptors | journal = J. Mol. Endocrinol. | volume = 28 | issue = 3 | pages = 149–52 | year = 2002 | pmid = 12063181 | doi = 10.1677/jme.0.0280149| url =https://cloudfront.escholarship.org/dist/prd/content/qt8qd4j1k2/qt8qd4j1k2.pdf | doi-access = free }}</ref><ref name="KuiperCarlsson1997">{{cite journal|last1=Kuiper|first1=George G. J. M.|last2=Carlsson|first2=Bo|last3=Grandien|first3=Kaj|last4=Enmark|first4=Eva|last5=Häggblad|first5=Johan|last6=Nilsson|first6=Stefan|last7=Gustafsson|first7=Jan-Åke|title=Comparison of the Ligand Binding Specificity and Transcript Tissue Distribution of Estrogen Receptors α and β|journal=Endocrinology|volume=138|issue=3|year=1997|pages=863–870|issn=0013-7227|doi=10.1210/endo.138.3.4979|pmid=9048584|doi-access=free}}</ref> It has approximately 3% and 7% of the [[affinity (pharmacology)|affinity]] of [[estradiol]] at the [[ERα]] and [[ERβ]], respectively.<ref name="pmid9048584">{{cite journal | vauthors = Kuiper GG, Carlsson B, Grandien K, Enmark E, Häggblad J, Nilsson S, Gustafsson JA | title = Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta | journal = Endocrinology | volume = 138 | issue = 3 | pages = 863–70 | year = 1997 | pmid = 9048584 | doi = 10.1210/endo.138.3.4979 | doi-access = free }}</ref> Unlike [[3α-androstanediol]], 3β-androstanediol does not bind to the [[GABAA receptor|GABA<sub>A</sub> receptor]].<ref name="ReddyJian2010">{{cite journal|last1=Reddy|first1=D. S.|last2=Jian|first2=K.|title=The Testosterone-Derived Neurosteroid Androstanediol Is a Positive Allosteric Modulator of GABAA Receptors|journal=Journal of Pharmacology and Experimental Therapeutics|volume=334|issue=3|year=2010|pages=1031–1041|issn=0022-3565|doi=10.1124/jpet.110.169854|pmid=20551294|pmc=2939675}}</ref>

3β-Androstanediol may be the primary endogenous [[ligand (biochemistry)|ligand]] of ERβ in the [[prostate gland]], and as a result of activation of the ERβ, 3β-androstanediol has [[antiproliferative]] effects against [[prostate cancer]] [[Cell (biology)|cell]]s.<ref name="pmid12370428">{{cite journal | vauthors = Weihua Z, Lathe R, Warner M, Gustafsson JA | title = An endocrine pathway in the prostate, ERbeta, AR, 5alpha-androstane-3beta,17beta-diol, and CYP7B1, regulates prostate growth | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 21 | pages = 13589–94 |date=October 2002 | pmid = 12370428 | pmc = 129718 | doi = 10.1073/pnas.162477299 | bibcode = 2002PNAS...9913589W | doi-access = free }}</ref> Through the ERβ, 3β-androstanediol positively regulates [[oxytocin]] [[neuron]]s and [[cell signaling|signaling]] in the [[paraventricular nucleus of hypothalamus]],<ref name="SharmaHanda2012">{{cite journal|last1=Sharma|first1=Dharmendra|last2=Handa|first2=Robert J.|last3=Uht|first3=Rosalie M.|title=The ERβ Ligand 5α-androstane, 3β,17β-diol (3β-diol) Regulates Hypothalamic Oxytocin (Oxt) Gene Expression|journal=Endocrinology|volume=153|issue=5|year=2012|pages=2353–2361|issn=0013-7227|doi=10.1210/en.2011-1002|pmc=3339641|pmid=22434086}}</ref><ref name="HiroiLacagnina2013">{{cite journal|last1=Hiroi|first1=Ryoko|last2=Lacagnina|first2=Anthony F.|last3=Hinds|first3=Laura R.|last4=Carbone|first4=David G.|last5=Uht|first5=Rosalie M.|last6=Handa|first6=Robert J.|title=The Androgen Metabolite, 5α-Androstane-3β,17β-Diol (3β-Diol), Activates the Oxytocin Promoter Through an Estrogen Receptor-β Pathway|journal=Endocrinology|volume=154|issue=5|year=2013|pages=1802–1812|issn=0013-7227|doi=10.1210/en.2012-2253|pmc=3628024|pmid=23515287}}</ref> and has been found to have [[antidepressant]],<ref name="HuangZhu2008">{{cite journal|last1=Huang|first1=Q|last2=Zhu|first2=H|last3=Fischer|first3=D|last4=Zhou|first4=J|title=An estrogenic effect of 5α-androstane-3β, 17β-diol on the behavioral response to stress and on CRH regulation|journal=Neuropharmacology|volume=54|issue=8|year=2008|pages=1233–1238|issn=0028-3908|doi=10.1016/j.neuropharm.2008.03.016|pmid=18457850|s2cid=9052079}}</ref> [[anxiolytic]],<ref name="FryeKoonce2008">{{cite journal|last1=Frye|first1=C|last2=Koonce|first2=C|last3=Edinger|first3=K|last4=Osborne|first4=D|last5=Walf|first5=A|title=Androgens with activity at estrogen receptor beta have anxiolytic and cognitive-enhancing effects in male rats and mice|journal=Hormones and Behavior|volume=54|issue=5|year=2008|pages=726–734|issn=0018-506X|doi=10.1016/j.yhbeh.2008.07.013|pmid=18775724|pmc=3623974}}</ref> [[nootropic|cognitive-enhancing]],<ref name="FryeKoonce2008" /> and [[stress relief|stress-relieving]] effects via this action.<ref name="HandaWeiser2009">{{cite journal|last1=Handa|first1=R. J.|last2=Weiser|first2=M. J.|last3=Zuloaga|first3=D. G.|title=A Role for the Androgen Metabolite, 5α-Androstane-3β,17β-Diol, in Modulating Oestrogen Receptor β-Mediated Regulation of Hormonal Stress Reactivity|journal=Journal of Neuroendocrinology|volume=21|issue=4|year=2009|pages=351–358|issn=0953-8194|doi=10.1111/j.1365-2826.2009.01840.x|pmc=2727750|pmid=19207807}}</ref><ref name="HandaSharma2011">{{cite journal|last1=Handa|first1=Robert J.|last2=Sharma|first2=Dharmendra|last3=Uht|first3=Rosalie|title=A Role for the Androgen Metabolite, 5alpha Androstane 3beta, 17beta Diol (3?-Diol) in the Regulation of the Hypothalamo-Pituitary?Adrenal Axis|journal=Frontiers in Endocrinology|volume=2|pages=65|year=2011|issn=1664-2392|doi=10.3389/fendo.2011.00065|pmc=3355903|pmid=22649380|doi-access=free}}</ref> 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.<ref name="HandaWeiser2009" /><ref name="HandaSharma2011" /><ref name="HandaPak2008">{{cite journal|last1=Handa|first1=Robert J.|last2=Pak|first2=Toni R.|last3=Kudwa|first3=Andrea E.|last4=Lund|first4=Trent D.|last5=Hinds|first5=Laura|title=An alternate pathway for androgen regulation of brain function: Activation of estrogen receptor beta by the metabolite of dihydrotestosterone, 5α-androstane-3β,17β-diol|journal=Hormones and Behavior|volume=53|issue=5|year=2008|pages=741–752|issn=0018-506X|doi=10.1016/j.yhbeh.2007.09.012|pmc=2430080|pmid=18067894}}</ref>

==Biochemistry==
{{Testosterone metabolism mini|align=right|caption=This diagram illustrates the [[metabolic pathway]]s involved in the [[metabolism]] of DHT in humans. In addition to the [[biotransformation|transformation]]s shown in the diagram, [[conjugation (biochemistry)|conjugation]] (e.g., [[sulfation]] and [[glucuronidation]]) occurs with DHT and [[metabolite]]s that have one or more available [[hydroxyl group|hydroxyl]] (–OH) [[functional group|group]]s.}}
3β-Androstanediol is a [[5α-reductase|5α-reduced]] and [[17β-Hydroxysteroid dehydrogenase|17β-hydroxy]]lated [[metabolite]] of [[dehydroepiandrosterone]] (DHEA) as well as a [[3β-hydroxysteroid dehydrogenase|3β-hydroxy]]lated metabolite of DHT (and by extension of [[testosterone]]).

A determination of the circulating levels of 3β-androstanediol in [[human]]s found [[concentration]]s of 239 ± 76 pg/ml and 82 ± 45 pg/ml of the compound in normal [[male]] and [[female]] [[serum (blood)|serum]], respectively.<ref name="pmid581118">{{cite journal | vauthors = Laband P, Tresguerres JA, Lisboa BP, Volkwein U, Tamm J | title = The determination of 5alpha-androstane-3alpha, 17beta-diol in human plasma by radioimmunoassay | journal = Acta Endocrinologica | volume = 88 | issue = 4 | pages = 778–86 |date=August 1978 | pmid = 581118 | doi = 10.1530/acta.0.0880778}}</ref>

3β-Androstanediol shows high affinity for [[sex hormone-binding globulin]] (SHBG), similar to that of DHT.<ref name="pmid25349334">{{cite journal | vauthors = Hong H, Branham WS, Ng HW, Moland CL, Dial SL, Fang H, Perkins R, Sheehan D, Tong W | title = 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 | journal = Toxicol. Sci. | volume = 143 | issue = 2 | pages = 333–48 | date = February 2015 | pmid = 25349334 | doi = 10.1093/toxsci/kfu231 | doi-access = free }}</ref>

==Chemistry==
3β-Androstanediol, also known as 5α-androstane-3β,17β-diol, is a [[natural product|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-alkylated|17α-substituted]] [[chemical derivative|derivative]] of 3β-androstanediol and is an estrogen similarly.<ref name="pmid13350363">{{cite journal | vauthors = Beyler AL, Clinton RO | title = Uterine growth stimulating and testicular growth suppressing activities of 17alpha-ethinylandrostane-3beta, 17beta-diol, its delta 5-analog and derivatives | journal = Proc. Soc. Exp. Biol. Med. | volume = 92 | issue = 2 | pages = 404–8 | date = June 1956 | pmid = 13350363 | doi = 10.3181/00379727-92-22493| s2cid = 87469965 }}</ref><ref name="pmid20814732">{{cite journal | vauthors = Ahlem C, Kennedy M, Page T, Bell D, Delorme E, Villegas S, Reading C, White S, Stickney D, Frincke J | title = 17α-alkynyl 3α, 17β-androstanediol non-clinical and clinical pharmacology, pharmacokinetics and metabolism | journal = Invest New Drugs | volume = 30 | issue = 1 | pages = 59–78 | date = February 2012 | pmid = 20814732 | doi = 10.1007/s10637-010-9517-0 | s2cid = 24785562 }}</ref>

==References==
{{Reflist}}


{{Steroid hormones}}
{{Estrogen receptor modulators}}

{{DEFAULTSORT:Androstanediol, 3β-}}

[[Category:5α-Reduced steroid metabolites]]
[[Category:Androstanes]]
[[Category:Experimental antidepressants]]
[[Category:Anxiolytics]]
[[Category:Estrogens]]
[[Category:Human metabolites]]
[[Category:Selective ERβ agonists]]