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3α-Androstanediol
Names
IUPAC name
5α-Androstane-3α,17β-diol
Systematic IUPAC name
(1S ,3aS ,3bR ,5aS ,7R ,9aS ,9bS ,11aS )-9a,11a-Dimethylhexadecahydro-1H -cyclopenta[a ]phenanthrene-1,7-diol
Other names
Hombreol
Identifiers
ChEBI
ChemSpider
ECHA InfoCard
100.015.862
UNII
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-KHOSGYARSA-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-KHOSGYARBM
C[C@]12CC[C@H]3[C@@H](CC[C@H]4C[C@H](O)CC[C@@]43C)[C@@H]1CC[C@@H]2O
Properties
C 19 H 32 O 2
Molar mass
292.463 g·mol−1
Except where otherwise noted, data are given for materials in their
standard state (at 25 °C [77 °F], 100 kPa).
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).
[1]
[2]
[3]
3α-Androstanediol is an
inhibitory
androstane
neurosteroid and weak
androgen and
estrogen .
[1]
[2]
[3]
As a neurosteroid, it acts as a potent
positive allosteric modulator of the
GABAA receptor ,
[4] and has been found to have
rewarding ,
[5]
[6]
anxiolytic ,
[7]
pro-sexual ,
[8] and
anticonvulsant effects.
[9]
[10] 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.
[5]
[6]
[7]
[10]
Relative to its isomer
3β-androstanediol , which is a potent
estrogen , 3α-androstanediol has substantially lower, though still significant
affinity for the
estrogen receptors , with a several-fold preference for
ERβ over
ERα .
[11]
[12] It has approximately 0.07% and 0.3% of the
affinity of
estradiol at the ERα and ERβ, respectively.
[13]
3α-Androstanediol shows high affinity for
sex hormone-binding globulin (SHBG), similar to that of
testosterone .
[14]
3α-Androstanediol, also known as 5α-androstane-3α,17β-diol, is a
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 .
[15]
^
a
b Reddy DS (2010). "Neurosteroids". Sex Differences in the Human Brain, their Underpinnings and Implications . Progress in Brain Research. Vol. 186. pp. 113–37.
doi :
10.1016/B978-0-444-53630-3.00008-7 .
ISBN
9780444536303 .
PMC
3139029 .
PMID
21094889 .
^
a
b Jin Y, Penning TM (March 2001). "Steroid 5alpha-reductases and 3alpha-hydroxysteroid dehydrogenases: key enzymes in androgen metabolism". Best Pract. Res. Clin. Endocrinol. Metab . 15 (1): 79–94.
doi :
10.1053/beem.2001.0120 .
PMID
11469812 .
^
a
b Penning TM, Bauman DR, Jin Y, Rizner TL (February 2007).
"Identification of the molecular switch that regulates access of 5alpha-DHT to the androgen receptor" . Mol. Cell. Endocrinol . 265–266: 77–82.
doi :
10.1016/j.mce.2006.12.007 .
PMC
1857325 .
PMID
17223255 .
^ Reddy DS, Jian K (September 2010).
"The testosterone-derived neurosteroid androstanediol is a positive allosteric modulator of GABAA receptors" . J. Pharmacol. Exp. Ther . 334 (3): 1031–41.
doi :
10.1124/jpet.110.169854 .
PMC
2939675 .
PMID
20551294 .
^
a
b Frye CA (February 2007).
"Some rewarding effects of androgens may be mediated by actions of its 5alpha-reduced metabolite 3alpha-androstanediol" . Pharmacol. Biochem. Behav . 86 (2): 354–67.
doi :
10.1016/j.pbb.2006.10.003 .
PMC
1857333 .
PMID
17112575 .
^
a
b Rosellini RA, Svare BB, Rhodes ME, Frye CA (November 2001). "The testosterone metabolite and neurosteroid 3alpha-androstanediol may mediate the effects of testosterone on conditioned place preference". Brain Res. Brain Res. Rev . 37 (1–3): 162–71.
doi :
10.1016/s0165-0173(01)00116-3 .
PMID
11744084 .
S2CID
44735355 .
^
a
b Fernández-Guasti A, Martínez-Mota L (September 2005). "Anxiolytic-like actions of testosterone in the burying behavior test: role of androgen and GABA-benzodiazepine receptors". Psychoneuroendocrinology . 30 (8): 762–70.
doi :
10.1016/j.psyneuen.2005.03.006 .
PMID
15919582 .
S2CID
3150411 .
^ Sánchez Montoya EL, Hernández L, Barreto-Estrada JL, Ortiz JG, Jorge JC (November 2010).
"The testosterone metabolite 3α-diol enhances female rat sexual motivation when infused in the nucleus accumbens shell" . J Sex Med . 7 (11): 3598–609.
doi :
10.1111/j.1743-6109.2010.01937.x .
PMC
4360968 .
PMID
20646182 .
^ Reddy DS (March 2004). "Anticonvulsant activity of the testosterone-derived neurosteroid 3alpha-androstanediol". NeuroReport . 15 (3): 515–8.
doi :
10.1097/00001756-200403010-00026 .
PMID
15094514 .
S2CID
29967602 .
^
a
b Reddy DS (2004). "Testosterone modulation of seizure susceptibility is mediated by neurosteroids 3alpha-androstanediol and 17beta-estradiol". Neuroscience . 129 (1): 195–207.
doi :
10.1016/j.neuroscience.2004.08.002 .
PMID
15489042 .
S2CID
54391883 .
^ 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; 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 .
^ 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 .
^ 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 .
^ Ahlem C, Kennedy M, Page T, Bell D, Delorme E, Villegas S, Reading C, White S, Stickney D, Frincke J (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 .
AR Tooltip Androgen receptor
Agonists
SARMs Tooltip Selective androgen receptor modulator Antagonists
GPRC6A
ER Tooltip Estrogen receptor
Agonists
Steroidal:
2-Hydroxyestradiol
2-Hydroxyestrone
3-Methyl-19-methyleneandrosta-3,5-dien-17β-ol
3α-Androstanediol
3α,5α-Dihydrolevonorgestrel
3β,5α-Dihydrolevonorgestrel
3α-Hydroxytibolone
3β-Hydroxytibolone
3β-Androstanediol
4-Androstenediol
4-Androstenedione
4-Fluoroestradiol
4-Hydroxyestradiol
4-Hydroxyestrone
4-Methoxyestradiol
4-Methoxyestrone
5-Androstenediol
7-Oxo-DHEA
7α-Hydroxy-DHEA
7α-Methylestradiol
7β-Hydroxyepiandrosterone
8,9-Dehydroestradiol
8,9-Dehydroestrone
8β-VE2
10β,17β-Dihydroxyestra-1,4-dien-3-one (DHED)
11β-Chloromethylestradiol
11β-Methoxyestradiol
15α-Hydroxyestradiol
16-Ketoestradiol
16-Ketoestrone
16α-Fluoroestradiol
16α-Hydroxy-DHEA
16α-Hydroxyestrone
16α-Iodoestradiol
16α-LE2
16β-Hydroxyestrone
16β,17α-Epiestriol (16β-hydroxy-17α-estradiol)
17α-Estradiol (
alfatradiol )
17α-Dihydroequilenin
17α-Dihydroequilin
17α-Epiestriol (16α-hydroxy-17α-estradiol)
17α-Ethynyl-3α-androstanediol
17α-Ethynyl-3β-androstanediol
17β-Dihydroequilenin
17β-Dihydroequilin
17β-Methyl-17α-dihydroequilenin
Abiraterone
Abiraterone acetate
Alestramustine
Almestrone
Anabolic steroids (e.g.,
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catechin ,
daidzein ,
daidzin ,
ECG ,
EGCG ,
epicatechin ,
equol ,
formononetin ,
glabrene ,
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genistein ,
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kaempferol ,
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digitoxin (
digitalis ),
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Resorcylic acid lactones (e.g.,
zearalanone ,
α-zearalenol ,
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zearalenone ,
zeranol (α-zearalanol) ,
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agnuside ,
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Mixed (
SERMs Tooltip Selective estrogen receptor modulators ) Antagonists
Coregulator-binding modulators:
ERX-11
GPER Tooltip G protein-coupled estrogen receptor
Agonists Antagonists Unknown
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gases Others/unsorted
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AA-29504
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Org 25,435
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valerenol )