View source for Androstenediol

{{Short description|Chemical compound}}
{{About|androstenediol the hormone|other uses|Androstenediol (disambiguation)}}
{{Distinguish|androstanedione|androstanediol|androstenedione|androstadienol}}
{{Drugbox
| verifiedrevid = 477224050
| IUPAC_name = (3''S'',8''R'',9''S'',10''R'',13''S'',14''S'',17''S'')-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1''H''-cyclopenta[''a'']phenanthrene-3,17-diol
| image = Androstendiol.svg
| width = 225px
| image2 = Androstenediol molecule ball.png
| width2 = 235px

<!--Clinical data-->
| tradename = 
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B / C / D / X -->
| pregnancy_category = 
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C -->
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_status = 
| routes_of_administration = [[Oral administration|By mouth]]
| class = [[Androgen]]; [[Anabolic steroid]]

<!--Pharmacokinetic data-->
| bioavailability = 
| protein_bound = 
| metabolism = 
| elimination_half-life = 
| excretion =

<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 521-17-5
| CAS_supplemental = 
| ATC_prefix = 
| ATC_suffix = 
| PubChem = 10634
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB01524
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 10188
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 95PS51EMXY
| KEGG = C04295
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 2710
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 440283
| synonyms = A5; Δ<sup>5</sup>-Diol; Androstenediol; Androst-5-ene-3β,17β-diol; Hermaphrodiol; HE2100

<!--Chemical data-->
| C=19 | H=30 | O=2
| SMILES = O[C@@H]4C/C3=C/C[C@@H]1[C@H](CC[C@@]2([C@@H](O)CC[C@@H]12)C)[C@@]3(C)CC4
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C19H30O2/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/h3,13-17,20-21H,4-11H2,1-2H3/t13-,14-,15-,16-,17-,18-,19-/m0/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = QADHLRWLCPCEKT-LOVVWNRFSA-N
}}

'''Androstenediol''', or '''5-androstenediol''' (abbreviated as '''A5''' or '''Δ<sup>5</sup>-diol'''), also known as '''androst-5-ene-3β,17β-diol''', is an [[endogenous]] weak [[androgen]] and [[estrogen]] [[steroid hormone]] and [[chemical intermediate|intermediate]] in the [[biosynthesis]] of [[testosterone]] from [[dehydroepiandrosterone]] (DHEA). It is closely related to [[androstenedione]] (androst-4-ene-3,17-dione).

==Biological activity==
Androstenediol is a direct [[metabolite]] of the most abundant [[steroid]] produced by the human [[adrenal cortex]], DHEA. It is less [[androgen]]ic than the related compound, [[4-androstenediol|Δ<sup>4</sup>-androstenediol]], and has been found to stimulate the [[immune system]]. When administered to [[rat]]s, androstenediol, ''[[in vivo]]'', has approximately 1.4% of the [[androgen]]icity of DHEA, 0.54% of the androgenicity of [[androstenedione]], and 0.21% of the androgenicity of testosterone.<ref>{{cite book | vauthors = Coffey DS | date = 1988 | chapter = Androgen action and the sex accessory tissues | veditors = Knobil E, Neill J | title = The Physiology of Reproduction. | publisher = Raven Press | location = New York | pages = 1081–1119 }}</ref>

Androstenediol possesses potent [[estrogen]]ic activity, similarly to DHEA and [[3β-androstanediol]].<ref name="HackenbergTurgetto1993">{{cite journal | vauthors = Hackenberg R, Turgetto I, Filmer A, Schulz KD | title = Estrogen and androgen receptor mediated stimulation and inhibition of proliferation by androst-5-ene-3 beta,17 beta-diol in human mammary cancer cells | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 46 | issue = 5 | pages = 597–603 | date = November 1993 | pmid = 8240982 | doi = 10.1016/0960-0760(93)90187-2 | s2cid = 54256515 }}</ref> It has approximately 6% and 17% 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 = 863–870 | date = March 1997 | pmid = 9048584 | doi = 10.1210/endo.138.3.4979 | doi-access = free }}</ref> Although androstenediol has far lower affinity for the ERs compared to the major estrogen [[estradiol]], it circulates at approximately 100-fold higher concentrations, and so is thought may play a significant role as an estrogen in the body.<ref name="Bradbury2007">{{cite book| vauthors = Bradbury R |title=Cancer|url=https://books.google.com/books?id=fdtDAAAAQBAJ&pg=PA43|date=30 January 2007|publisher=Springer Science & Business Media|isbn=978-3-540-33120-9|pages=43–}}</ref>

{{Affinities of estrogen receptor ligands for the ERα and ERβ}}

==Chemistry==
{{See also|List of androgens/anabolic steroids#Testosterone derivatives|List of androgen esters#Esters of other natural AAS}}

Androstenediol, also known as androst-5-ene-3β,17β-diol, is a [[natural product|naturally occurring]] [[androstane]] [[steroid]].<ref name="Elks2014">{{cite book| vauthors = Elks J |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA86|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=86–}}</ref> It is closely related structurally to [[androstenedione]] (A4; androst-4-ene-3,17-dione), [[dehydroepiandrosterone]] (DHEA; androst-5-en-3β-ol-17-one), and [[testosterone]] (androst-4-en-17β-ol-3-one), as well as to [[3β-androstanediol]] (5α-androstane-3β,17β-diol).<ref name="Elks2014" />

[[Chemical derivative|Derivative]]s and [[structural analog|analogue]]s of androstenediol, such as the [[17α-alkylated|17α-substituted]] [[methandriol]] (17α-methylandrostenediol) and [[ethinylandrostenediol]] (17α-ethynylandrostenediol) as well as the naturally occurring [[19-norandrostane]] derivative [[19-nor-5-androstenediol|norandostenediol]] (19-nor-5-androstenediol), have been [[chemical synthesis|synthesized]] and studied. Methandriol and its [[methandriol ester|ester]]s are [[androgen]]s and [[anabolic steroid]]s while ethinylandrostenediol is an estrogen.

==Research==

===Radiation countermeasure===
Androstenediol has been investigated for use as a radiation countermeasure. Its value as a radiation countermeasure is based mainly on its stimulation of production of [[white blood cell]]s and [[platelet]]s.<ref name="IJI" /> Its potential use as a [[ionizing radiation|radiation]] countermeasure was developed by the [[Armed Forces Radiobiology Research Institute]] (AFRRI) and subsequently studied by AFRRI and Hollis-Eden Pharmaceuticals under the proposed brand name Neumune for the treatment of [[radiation poisoning|acute radiation syndrome]].<ref name="IJI">{{cite journal | vauthors = Whitnall MH, Elliott TB, Harding RA, Inal CE, Landauer MR, Wilhelmsen CL, McKinney L, Miner VL, Jackson WE 3rd, Loria RM, Ledney GD, Seed TM | year = 2000 | title = Androstenediol stimulates myelopoiesis and enhances resistance to infection in gamma-irradiated mice | journal = Int. J. Immunopharmacol. | volume = 22 | issue = 1 | pages = 1–14 | pmid = 10684984 | doi=10.1016/s0192-0561(99)00059-4}}</ref><ref>{{cite journal | vauthors = Grace MB, Singh VK, Rhee JG, Jackson WE 3rd, Kao TC, Whitnall MH | year = 2012 | title = 5-AED enhances survival of irradiated mice in a G-CSF-dependent manner, stimulates innate immune cell function, reduces radiation-induced DNA damage and induces genes that modulate cell cycle progression and apoptosis | journal = J. Radiat. Res. | volume = 53 | issue = 6 | pages = 840–853 | pmid = 22843381 | doi = 10.1093/jrr/rrs060 | pmc=3483857}}</ref>

The [[clinical trial]]s with [[rhesus monkey]]s were successful. According to the Hollis-Eden report, only 12.5% of the 40 Neumune-treated animals died versus 32.5% in the [[placebo]] group.<ref>[http://biz.yahoo.com/bw/070226/20070226005559.html?.v=1 Hollis-Eden Pharmaceuticals Reports Publication of Results Demonstrating the Ability of NEUMUNE(R) to Increase Survival in a Primate Model of Lethal Radiation Injury], February 26, 2007.</ref>

Hollis-Eden had applied for a contract from the U.S. Government under the BioShield Request for Proposals (RFP) for radiation countermeasures. After being encouraged for 2.5 years that Neumune was in the competitive range, on March 9, 2007, the RFP was canceled by [[United States Department of Health and Human Services|HHS]]. According to HHS, "the product was no longer in the competitive range".<ref>[http://www.smartmoney.com/onedaywonder/index.cfm?story=20070308&src=fb&nav=RSS20 Government Nukes Hollis-Eden's Radiation Drug], by Val Brickates Kennedy and Angela Moore, March 8, 2007</ref><ref>[http://new.quote.com/stocks/story.action?id=DTM068x6797 US cancels radiation contract with Hollis-Eden] {{webarchive|url=https://archive.today/20070912210559/http://new.quote.com/stocks/story.action?id=DTM068x6797 |date=2007-09-12 }}, March 9, 2007</ref> No further explanation was given. As a result, Hollis-Eden has now withdrawn from the radiation countermeasure field.

==Additional images==
[[File:Steroidogenesis.svg|thumb|left|350px|[[Steroidogenesis]], with androstenediol at bottom left.]]
{{Clear}}

==References==
{{Reflist|30em}}


{{Endogenous steroids}}
{{Navboxes
| title = [[Biological activity]]
| titlestyle = background:#ccccff
| list1 = 
{{Androgen receptor modulators}}
{{Estrogen receptor modulators}}
{{Xenobiotic-sensing receptor modulators}}
}}

[[Category:Anabolic–androgenic steroids]]
[[Category:Androstanes]]
[[Category:Estrogens]]
[[Category:Pregnane X receptor agonists]]
[[Category:Selective ERβ agonists]]