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3α あるふぁ -Androstanediol
Names
IUPAC name
5α あるふぁ -Androstane-3α あるふぁ ,17β べーた -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 あるふぁ -Androstanediol also known as 5α あるふぁ -androstane-3α あるふぁ ,17β べーた -diol and sometimes shortened in the literature to 3α あるふぁ -diol , is an endogenous steroid hormone and neurosteroid and a metabolite of androgens like dihydrotestosterone (DHT).[ 1] [ 2] [ 3]
Biological activity [ edit ]
3α あるふぁ -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 あるふぁ -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 べーた -androstanediol , which is a potent estrogen , 3α あるふぁ -androstanediol has substantially lower, though still significant affinity for the estrogen receptors , with a several-fold preference for ERβ べーた over ERα あるふぁ .[ 11] [ 12] It has approximately 0.07% and 0.3% of the affinity of estradiol at the ERα あるふぁ and ERβ べーた , respectively.[ 13]
3α あるふぁ -Androstanediol shows high affinity for sex hormone-binding globulin (SHBG), similar to that of testosterone .[ 14]
3α あるふぁ -Androstanediol, also known as 5α あるふぁ -androstane-3α あるふぁ ,17β べーた -diol, is a naturally occurring androstane steroid and a structural analogue of DHT (5α あるふぁ -androstan-17β べーた -ol-3-one). A notable positional isomer of 3α あるふぁ -androstanediol is 3β べーた -androstanediol .
An orally active synthetic analogue of 3α あるふぁ -androstanediol, 17α あるふぁ -ethynyl-3α あるふぁ -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 あるふぁ -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 あるふぁ and β べーた " . 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 あるふぁ -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 あるふぁ -alkynyl 3α あるふぁ , 17β べーた -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 べーた -ol
3α あるふぁ -Androstanediol
3α あるふぁ ,5α あるふぁ -Dihydrolevonorgestrel
3β べーた ,5α あるふぁ -Dihydrolevonorgestrel
3α あるふぁ -Hydroxytibolone
3β べーた -Hydroxytibolone
3β べーた -Androstanediol
4-Androstenediol
4-Androstenedione
4-Fluoroestradiol
4-Hydroxyestradiol
4-Hydroxyestrone
4-Methoxyestradiol
4-Methoxyestrone
5-Androstenediol
7-Oxo-DHEA
7α あるふぁ -Hydroxy-DHEA
7α あるふぁ -Methylestradiol
7β べーた -Hydroxyepiandrosterone
8,9-Dehydroestradiol
8,9-Dehydroestrone
8β べーた -VE2
10β べーた ,17β べーた -Dihydroxyestra-1,4-dien-3-one (DHED)
11β べーた -Chloromethylestradiol
11β べーた -Methoxyestradiol
15α あるふぁ -Hydroxyestradiol
16-Ketoestradiol
16-Ketoestrone
16α あるふぁ -Fluoroestradiol
16α あるふぁ -Hydroxy-DHEA
16α あるふぁ -Hydroxyestrone
16α あるふぁ -Iodoestradiol
16α あるふぁ -LE2
16β べーた -Hydroxyestrone
16β べーた ,17α あるふぁ -Epiestriol (16β べーた -hydroxy-17α あるふぁ -estradiol)
17α あるふぁ -Estradiol (alfatradiol )
17α あるふぁ -Dihydroequilenin
17α あるふぁ -Dihydroequilin
17α あるふぁ -Epiestriol (16α あるふぁ -hydroxy-17α あるふぁ -estradiol)
17α あるふぁ -Ethynyl-3α あるふぁ -androstanediol
17α あるふぁ -Ethynyl-3β べーた -androstanediol
17β べーた -Dihydroequilenin
17β べーた -Dihydroequilin
17β べーた -Methyl-17α あるふぁ -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 べーた -epiestriol, 16β べーた -hydroxy-17β べーた -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 べーた -sitosterol , campesterol , stigmasterol )
Resorcylic acid lactones (e.g., zearalanone , α あるふぁ -zearalenol , β べーた -zearalenol , zearalenone , zeranol (α あるふぁ -zearalanol) , taleranol (teranol, β べーた -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
Alcohols Barbiturates Benzodiazepines Carbamates Flavonoids Imidazoles Kava constituentsMonoureides Neuroactive steroids Nonbenzodiazepines Phenols Piperidinediones Pyrazolopyridines Quinazolinones Volatiles /gases Others/unsorted
3-Hydroxybutanal
α あるふぁ -EMTBL
AA-29504
Alogabat
Avermectins (e.g., ivermectin )
Bromide compounds (e.g., lithium bromide , potassium bromide , sodium bromide )
Carbamazepine
Chloralose
Chlormezanone
Clomethiazole
Darigabat
DEABL
Deuterated etifoxine
Dihydroergolines (e.g., dihydroergocryptine , dihydroergosine , dihydroergotamine , ergoloid (dihydroergotoxine) )
DS2
Efavirenz
Etazepine
Etifoxine
Fenamates (e.g., flufenamic acid , mefenamic acid , niflumic acid , tolfenamic acid )
Fluoxetine
Flupirtine
Hopantenic acid
KRM-II-81
Lanthanum
Lavender oil
Lignans (e.g., 4-O-methylhonokiol , honokiol , magnolol , obovatol )
Loreclezole
Menthyl isovalerate (validolum)
Monastrol
Niacin
Niacinamide
Org 25,435
Phenytoin
Propanidid
Retigabine (ezogabine)
Safranal
Seproxetine
Stiripentol
Sulfonylalkanes (e.g., sulfonmethane (sulfonal) , tetronal , trional )
Terpenoids (e.g., borneol )
Topiramate
Valerian constituents (e.g., isovaleric acid , isovaleramide , valerenic acid , valerenol )