3α-Androstanediolのソースを表示

{{Chembox
| ImageFile = 3alpha-Androstanediol.svg
| ImageClass = skin-invert
| ImageSize = 250px
| IUPACName = 5α-Androstane-3α,17β-diol
| SystematicName = (1''S'',3a''S'',3b''R'',5a''S'',7''R'',9a''S'',9b''S'',11a''S'')-9a,11a-Dimethylhexadecahydro-1''H''-cyclopenta[''a'']phenanthrene-1,7-diol
| OtherNames = Hombreol
|Section1={{Chembox Identifiers
| CASNo = 1852-53-5
| CASNo_Ref = {{cascite|correct|CAS}}
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = J34MX0M30Y
| PubChem = 15818
| SMILES = C[C@]12CC[C@H]3[C@@H](CC[C@H]4C[C@H](O)CC[C@@]43C)[C@@H]1CC[C@@H]2O
| ChemSpiderID = 15039
| ChEBI = 36713
| 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-KHOSGYARBM
| 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-KHOSGYARSA-N
  }}
|Section2={{Chembox Properties
| C=19 | H=32 | O=2
| Appearance=
| Density=
| MeltingPt=
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| Solubility=
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|Section3={{Chembox Hazards
| MainHazards=
| FlashPt=
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}}

'''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 [[androgen]]s like [[dihydrotestosterone]] (DHT).<ref name="pmid21094889">{{cite book | author = Reddy DS | title = Sex Differences in the Human Brain, their Underpinnings and Implications | chapter = Neurosteroids | volume = 186 | pages = 113–37 | year = 2010 | pmid = 21094889 | pmc = 3139029 | doi = 10.1016/B978-0-444-53630-3.00008-7 | series = Progress in Brain Research | isbn = 9780444536303 }}</ref><ref name="pmid11469812">{{cite journal |vauthors=Jin Y, Penning TM | title = Steroid 5alpha-reductases and 3alpha-hydroxysteroid dehydrogenases: key enzymes in androgen metabolism | journal = Best Pract. Res. Clin. Endocrinol. Metab. | volume = 15 | issue = 1 | pages = 79–94 |date=March 2001  | pmid = 11469812 | doi = 10.1053/beem.2001.0120 }}</ref><ref name="pmid17223255">{{cite journal |vauthors=Penning TM, Bauman DR, Jin Y, Rizner TL | title = Identification of the molecular switch that regulates access of 5alpha-DHT to the androgen receptor | journal = Mol. Cell. Endocrinol. | volume = 265-266 | pages = 77–82 |date=February 2007  | pmid = 17223255 | pmc = 1857325 | doi = 10.1016/j.mce.2006.12.007 }}</ref>

==Biological activity==
3α-Androstanediol is an [[inhibitory postsynaptic potential|inhibitory]] [[androstane]] [[neurosteroid]] and weak [[androgen]] and [[estrogen]].<ref name="pmid21094889" /><ref name="pmid11469812" /><ref name="pmid17223255" />

As a neurosteroid, it acts as a potent [[positive allosteric modulator]] of the [[GABAA receptor|GABA<sub>A</sub> receptor]],<ref name="pmid20551294">{{cite journal |vauthors=Reddy DS, Jian K | title = The testosterone-derived neurosteroid androstanediol is a positive allosteric modulator of GABAA receptors | journal = J. Pharmacol. Exp. Ther. | volume = 334 | issue = 3 | pages = 1031–41 |date=September 2010  | pmid = 20551294 | pmc = 2939675 | doi = 10.1124/jpet.110.169854 }}</ref> and has been found to have [[pleasure|rewarding]],<ref name="pmid17112575">{{cite journal | author = Frye CA | title = Some rewarding effects of androgens may be mediated by actions of its 5alpha-reduced metabolite 3alpha-androstanediol | journal = Pharmacol. Biochem. Behav. | volume = 86 | issue = 2 | pages = 354–67 |date=February 2007  | pmid = 17112575 | pmc = 1857333 | doi = 10.1016/j.pbb.2006.10.003 }}</ref><ref name="pmid11744084">{{cite journal |vauthors=Rosellini RA, Svare BB, Rhodes ME, Frye CA | title = The testosterone metabolite and neurosteroid 3alpha-androstanediol may mediate the effects of testosterone on conditioned place preference | journal = Brain Res. Brain Res. Rev. | volume = 37 | issue = 1–3 | pages = 162–71 |date=November 2001  | pmid = 11744084 | doi = 10.1016/s0165-0173(01)00116-3| s2cid = 44735355 }}</ref> [[anxiolytic]],<ref name="pmid15919582">{{cite journal |vauthors=Fernández-Guasti A, Martínez-Mota L | s2cid = 3150411 | title = Anxiolytic-like actions of testosterone in the burying behavior test: role of androgen and GABA-benzodiazepine receptors | journal = Psychoneuroendocrinology | volume = 30 | issue = 8 | pages = 762–70 |date=September 2005  | pmid = 15919582 | doi = 10.1016/j.psyneuen.2005.03.006 }}</ref> [[aphrodisiac|pro-sexual]],<ref name="pmid20646182">{{cite journal |vauthors=Sánchez Montoya EL, Hernández L, Barreto-Estrada JL, Ortiz JG, Jorge JC | title = The testosterone metabolite 3α-diol enhances female rat sexual motivation when infused in the nucleus accumbens shell | journal = J Sex Med | volume = 7 | issue = 11 | pages = 3598–609 |date=November 2010  | pmid = 20646182 | doi = 10.1111/j.1743-6109.2010.01937.x | pmc=4360968}}</ref> and [[anticonvulsant]] effects.<ref name="pmid15094514">{{cite journal | author = Reddy DS | s2cid = 29967602 | title = Anticonvulsant activity of the testosterone-derived neurosteroid 3alpha-androstanediol | journal = NeuroReport | volume = 15 | issue = 3 | pages = 515–8 |date=March 2004  | pmid = 15094514 | doi = 10.1097/00001756-200403010-00026}}</ref><ref name="pmid15489042">{{cite journal | author = Reddy DS | s2cid = 54391883 | title = Testosterone modulation of seizure susceptibility is mediated by neurosteroids 3alpha-androstanediol and 17beta-estradiol | journal = Neuroscience | volume = 129 | issue = 1 | pages = 195–207 | year = 2004 | pmid = 15489042 | doi = 10.1016/j.neuroscience.2004.08.002 }}</ref> As androgens such as [[testosterone]] and DHT are known to have many of the same effects as 3α-diol and are converted into it ''in vivo'', it is thought that this compound may in part be responsible for said effects.<ref name="pmid17112575" /><ref name="pmid11744084" /><ref name="pmid15919582" /><ref name="pmid15489042" />

Relative to its isomer [[3β-androstanediol]], which is a potent [[estrogen]], 3α-androstanediol has substantially lower, though still significant [[affinity (pharmacology)|affinity]] for the [[estrogen receptor]]s, with a several-fold preference for [[ERβ]] over [[ERα]].<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 0.07% and 0.3% 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>

==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.}}

3α-Androstanediol shows high affinity for [[sex hormone-binding globulin]] (SHBG), similar to that of [[testosterone]].<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==
{{See also|List of neurosteroids}}

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

An orally active synthetic analogue of 3α-androstanediol, [[17α-ethynyl-3α-androstanediol]] (HE-3235, Apoptone), was formerly under investigation for the treatment of [[prostate cancer]] and [[breast cancer]].<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 | s2cid = 24785562 | 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 | year = 2012 | pmid = 20814732 | doi = 10.1007/s10637-010-9517-0 }}</ref>

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==References==
{{Reflist}}


{{Endogenous steroids}}
{{Androgen receptor modulators}}
{{Estrogen receptor modulators}}
{{GABAA receptor positive modulators}}

{{DEFAULTSORT:Androstanediol, 3α-}}

[[Category:5α-Reduced steroid metabolites]]
[[Category:Anabolic–androgenic steroids]]
[[Category:Androstanes]]
[[Category:Estrogens]]
[[Category:Human metabolites]]
[[Category:Neurosteroids]]
[[Category:GABAA receptor positive allosteric modulators]]
[[Category:Selective ERβ agonists]]