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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
ChEMBL
ChemSpider
ECHA InfoCard
100.008.487
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-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
C 19 H 32 O 2
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).
Chemical compound
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).
Biological activity
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
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
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
^ 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.
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S2CID
197144530 .
^ C.Y. Cheng (24 October 2009).
Molecular Mechanisms in Spermatogenesis . Springer Science & 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
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^ 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 :
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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 .
^ 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 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 .
^ 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 .
^ 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 .
^
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, 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 .
^
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, 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 .
^ 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 α-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). "17α-alkynyl 3α, 17β-androstanediol non-clinical and clinical pharmacology, pharmacokinetics and metabolism". Invest New Drugs . 30 (1): 59–78.
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10.1007/s10637-010-9517-0 .
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S2CID
24785562 .
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.,
testosterone and
esters ,
methyltestosterone ,
metandienone (methandrostenolone) ,
nandrolone and
esters , many others; via estrogenic metabolites)
Atrimustine
Bolandiol
Bolandiol dipropionate
Butolame
Clomestrone
Cloxestradiol
Conjugated estriol
Conjugated estrogens
Cyclodiol
Cyclotriol
DHEA
DHEA-S
ent -Estradiol
Epiestriol (16β-epiestriol, 16β-hydroxy-17β-estradiol)
Epimestrol
Equilenin
Equilin
ERA-63 (ORG-37663)
Esterified estrogens
Estetrol
Estradiol
Estramustine
Estramustine phosphate
Estrapronicate
Estrazinol
Estriol
Estrofurate
Estrogenic substances
Estromustine
Estrone
Etamestrol (eptamestrol)
Ethinylandrostenediol
Ethinylestradiol
Ethinylestriol
Ethylestradiol
Etynodiol
Etynodiol diacetate
Hexolame
Hippulin
Hydroxyestrone diacetate
Lynestrenol
Lynestrenol phenylpropionate
Mestranol
Methylestradiol
Moxestrol
Mytatrienediol
Nilestriol
Norethisterone
Noretynodrel
Orestrate
Pentolame
Prodiame
Prolame
Promestriene
RU-16117
Quinestradol
Quinestrol
Tibolone
Xenoestrogens:
Anise -related (e.g.,
anethole ,
anol ,
dianethole ,
dianol ,
photoanethole )
Chalconoids (e.g.,
isoliquiritigenin ,
phloretin ,
phlorizin (phloridzin) ,
wedelolactone )
Coumestans (e.g.,
coumestrol ,
psoralidin )
Flavonoids (incl.
7,8-DHF ,
8-prenylnaringenin ,
apigenin ,
baicalein ,
baicalin ,
biochanin A ,
calycosin ,
catechin ,
daidzein ,
daidzin ,
ECG ,
EGCG ,
epicatechin ,
equol ,
formononetin ,
glabrene ,
glabridin ,
genistein ,
genistin ,
glycitein ,
kaempferol ,
liquiritigenin ,
mirificin ,
myricetin ,
naringenin ,
penduletin ,
pinocembrin ,
prunetin ,
puerarin ,
quercetin ,
tectoridin ,
tectorigenin )
Lavender oil
Lignans (e.g.,
enterodiol ,
enterolactone ,
nyasol (cis -hinokiresinol) )
Metalloestrogens (e.g.,
cadmium )
Pesticides (e.g.,
alternariol ,
dieldrin ,
endosulfan ,
fenarimol ,
HPTE ,
methiocarb ,
methoxychlor ,
triclocarban ,
triclosan )
Phytosteroids (e.g.,
digitoxin (
digitalis ),
diosgenin ,
guggulsterone )
Phytosterols (e.g.,
β-sitosterol ,
campesterol ,
stigmasterol )
Resorcylic acid lactones (e.g.,
zearalanone ,
α-zearalenol ,
β-zearalenol ,
zearalenone ,
zeranol (α-zearalanol) ,
taleranol (teranol, β-zearalanol) )
Steroid -like (e.g.,
deoxymiroestrol ,
miroestrol )
Stilbenoids (e.g.,
resveratrol ,
rhaponticin )
Synthetic xenoestrogens (e.g.,
alkylphenols ,
bisphenols (e.g.,
BPA ,
BPF ,
BPS ),
DDT ,
parabens ,
PBBs ,
PHBA ,
phthalates ,
PCBs )
Others (e.g.,
agnuside ,
rotundifuran )
Mixed (
SERMs Tooltip Selective estrogen receptor modulators ) Antagonists
Coregulator-binding modulators:
ERX-11
GPER Tooltip G protein-coupled estrogen receptor
Agonists Antagonists Unknown