Canmetcon
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Record Information
Version2.0
Creation Date2014-09-11 05:14:48 UTC
Update Date2014-12-24 20:26:56 UTC
Accession NumberT3D4751
Identification
Common NameDihydrotestosterone
ClassSmall Molecule
DescriptionDihydrotestosterone is a potent androgenic metabolite of testosterone. Dihydrotestosterone (DHT) is generated by a 5-alpha reduction of testosterone. Unlike testosterone, DHT cannot be aromatized to estradiol therefore DHT is considered a pure androgenic steroid. -- Pubchem; Dihydrotestosterone (DHT) (INN: androstanolone) is a biologically active metabolite of the hormone testosterone, formed primarily in the prostate gland, testes, hair follicles, and adrenal glands by the enzyme 5-alpha-reductase by means of reducing the alpha 4,5 double-bond. Dihydrotestosterone belongs to the class of compounds called androgens, also commonly called androgenic hormones or testoids. DHT is thought to be approximately 30 times more potent than testosterone because of increased affinity to the androgen receptor. -- Wikipedia.
Compound Type
  • Androgen
  • Animal Toxin
  • Drug
  • Food Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
  • Steroid
Chemical Structure
Thumb
Synonyms
Synonym
(5a,17b)-17-Hydroxyandrostan-3-one
(5alpha,17beta)-17-hydroxyandrostan-3-one
17-Hydroxy-androstan-3-one
17-Hydroxyandrostan-3-one
17b-Hydroxy-3-androstanone
17beta-hydroxy-5alpha-androstan-3-one
17beta-Hydroxy-5alpha-androstane-3-one
17beta-Hydroxyandrostan-3-one
4,5a-Dihydrotestosterone
4-Dihydrotestosterone
5-a-Androstanolone
5-alpha-Androstanolone
5.alpha.-Dihydrotestosterone
5a-Androstan-17b-ol-3-one
5A-Androstan-3-on-17B-ol
5a-Dihydrotestosterone
5alpha dihydrotestosterone
5alpha-androstan-17beta-ol-3-one
5alpha-Dihydrotestosterone
5B-Androstan-3-on-17B-ol
Anaboleen
Anabolex
Anaprotin
Andractim
Androlone
Androstalone
Androstan-17b-ol-3-one
Androstan-17beta-ol-3-one
Androstanolone
Cristerona MB
DHT
Drolban
Neodrol
Proteina
Protona
Stanaprol
Stanolone
Stanorone
Chemical FormulaC19H30O2
Average Molecular Mass290.440 g/mol
Monoisotopic Mass290.225 g/mol
CAS Registry Number521-18-6
IUPAC Name(1S,2S,7S,10R,11S,14S,15S)-14-hydroxy-2,15-dimethyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadecan-5-one
Traditional Namedihydrotestosterone
SMILES[H][C@]1(O)CC[C@@]2([H])[C@]3([H])CC[C@@]4([H])CC(=O)CC[C@]4(C)[C@@]3([H])CC[C@]12C
InChI IdentifierInChI=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/h12,14-17,21H,3-11H2,1-2H3/t12-,14-,15-,16-,17-,18-,19-/m0/s1
InChI KeyInChIKey=NVKAWKQGWWIWPM-ABEVXSGRSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as androgens and derivatives. These are 3-hydroxylated C19 steroid hormones. They are known to favor the development of masculine characteristics. They also show profound effects on scalp and body hair in humans.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassAndrostane steroids
Direct ParentAndrogens and derivatives
Alternative Parents
Substituents
  • Androgen-skeleton
  • 3-oxosteroid
  • 3-oxo-5-alpha-steroid
  • 17-hydroxysteroid
  • Oxosteroid
  • Hydroxysteroid
  • Cyclic alcohol
  • Cyclic ketone
  • Secondary alcohol
  • Ketone
  • Organic oxygen compound
  • Organooxygen compound
  • Hydrocarbon derivative
  • Carbonyl group
  • Organic oxide
  • Alcohol
  • Aliphatic homopolycyclic compound
Molecular FrameworkAliphatic homopolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Endoplasmic reticulum
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Adipose Tissue
  • Adrenal Cortex
  • Adrenal Gland
  • Fibroblasts
  • Gonads
  • Hair
  • Kidney
  • Liver
  • Muscle
  • Myelin
  • Neuron
  • Prostate
  • Skin
  • Testes
  • Thyroid Gland
Pathways
NameSMPDB LinkKEGG Link
Androgen and Estrogen MetabolismSMP00068 map00150
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point181°C
Boiling PointNot Available
Solubility525 mg/mL at 25°C
LogP3.55
Predicted Properties
PropertyValueSource
Water Solubility0.01 g/LALOGPS
logP3.37ALOGPS
logP3.41ChemAxon
logS-4.5ALOGPS
pKa (Strongest Acidic)19.38ChemAxon
pKa (Strongest Basic)-0.88ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity83.6 m³·mol⁻¹ChemAxon
Polarizability34.69 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-015c-8970000000-ef0c6a4fd9c52be30284View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-001l-1790000000-60cff73adc796876d469View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-015c-8970000000-ef0c6a4fd9c52be30284View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-001l-1790000000-60cff73adc796876d469View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-03gj-0390000000-9eeab8ff981af1be878cView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-001j-2129000000-dbb4c264166c851e22c1View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00dl-0190000000-32b12edcbd16045a4a2eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00dl-0390000000-a2704bedea3c7bf92d65View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-016r-2790000000-d1a3cc2c786b582339b3View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-0090000000-62e8fc46490b14aee68aView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000i-0090000000-d712d8c85325f4935c06View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-05fu-2190000000-d8e9f38bc70955a04aeaView in MoNA
MSMass Spectrum (Electron Ionization)splash10-000x-9870000000-f6d80b2a53942c9af50bView in MoNA
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
Toxicity Profile
Route of ExposureBioavailability is very low (0-2%) following oral administration.
Mechanism of ToxicityNot Available
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesDihydrotestosterone is an endogenously produced metabolite found in the human body. It is used in metabolic reactions, catabolic reactions or waste generation.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB02901
HMDB IDHMDB02961
PubChem Compound ID10635
ChEMBL IDNot Available
ChemSpider ID14
KEGG IDC03917
UniProt IDNot Available
OMIM ID
ChEBI ID16330
BioCyc ID17-BETA-HYDROXY-5ALPHA-ANDROSTAN-3-O
CTD IDNot Available
Stitch IDNot Available
PDB IDDHT
ACToR IDNot Available
Wikipedia LinkDihydrotestosterone
References
Synthesis Reference

A. Glenn Braswell, Aftab J. Ahmed, “Composition for inhibiting production of dihydrotestosterone to treat benign prostate hyperplasia.” U.S. Patent US6264996, issued October, 1996.

MSDSLink
General References
  1. Choi MH, Kim JN, Chung BC: Rapid HPLC-electrospray tandem mass spectrometric assay for urinary testosterone and dihydrotestosterone glucuronides from patients with benign prostate hyperplasia. Clin Chem. 2003 Feb;49(2):322-5. [12560362 ]
  2. Tincello DG, Saunders PT, Hodgins MB, Simpson NB, Edwards CR, Hargreaves TB, Wu FC: Correlation of clinical, endocrine and molecular abnormalities with in vivo responses to high-dose testosterone in patients with partial androgen insensitivity syndrome. Clin Endocrinol (Oxf). 1997 Apr;46(4):497-506. [9196614 ]
  3. Farthing MJ, Rees LH, Edwards CR, Dawson AM: Male gonadal function in coeliac disease: 2. Sex hormones. Gut. 1983 Feb;24(2):127-35. [6682819 ]
  4. Aganovic I, Alac M, Cabrijan T, Grizelj V, Korsic M, Misjak-Vitez M, Reiner Z, Suchanek E, Simunic V, Zjacic-Rotkvic V: [National consensus on hyperandrogenemia]. Lijec Vjesn. 1996 Sep;118(9):189-90. [9011736 ]
  5. Clark RV, Hermann DJ, Cunningham GR, Wilson TH, Morrill BB, Hobbs S: Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5alpha-reductase inhibitor. J Clin Endocrinol Metab. 2004 May;89(5):2179-84. [15126539 ]
  6. Sato T, Sonoda T, Itami S, Takayasu S: Predominance of type I 5alpha-reductase in apocrine sweat glands of patients with excessive or abnormal odour derived from apocrine sweat (osmidrosis). Br J Dermatol. 1998 Nov;139(5):806-10. [9892945 ]
  7. Christiansen K, Knussmann R: Androgen levels and components of aggressive behavior in men. Horm Behav. 1987 Jun;21(2):170-80. [3610056 ]
  8. Hammond GL, Leinonen P, Bolton NJ, Vihko R: Measurement of sex hormone binding globulin in human amniotic fluid: its relationship to protein and testosterone concentrations, and fetal sex. Clin Endocrinol (Oxf). 1983 Apr;18(4):377-84. [6683603 ]
  9. Gratterola R: Anovulation and increased androgenic activity as breast cancer risk in women with fibrocystic disease of the breast. Cancer Res. 1978 Sep;38(9):3051-4. [679211 ]
  10. Boccon-Gibod L, Laudat MH, Guiban D, Steg A: Hormonal consequences of orchidectomy for carcinoma of the prostate. With special reference to the measurement of free testosterone in saliva and prostatic dihydrotestosterone levels. Eur Urol. 1988;15(1-2):99-102. [3215246 ]
  11. Misao R, Itoh N, Mori H, Fujimoto J, Tamaya T: Sex hormone-binding globulin mRNA levels in human uterine endometrium. Eur J Endocrinol. 1994 Dec;131(6):623-9. [7804446 ]
  12. Toscano V, Horton R: Circulating dihydrotestosterone may not reflect peripheral formation. J Clin Invest. 1987 Jun;79(6):1653-8. [3584464 ]
  13. Pineiro V, Casabiell X, Peino R, Lage M, Camina JP, Menendez C, Baltar J, Dieguez C, Casanueva F: Dihydrotestosterone, stanozolol, androstenedione and dehydroepiandrosterone sulphate inhibit leptin secretion in female but not in male samples of omental adipose tissue in vitro: lack of effect of testosterone. J Endocrinol. 1999 Mar;160(3):425-32. [10076188 ]
  14. Dawood MY, Saxena BB: Testosterone and dihydrotestosterone in maternal and cord blood and in amniotic fluid. Am J Obstet Gynecol. 1977 Sep 1;129(1):37-42. [900166 ]
  15. Geller J, Candari CD: Comparison of dihydrotestosterone levels in prostatic cancer metastases and primary prostate cancer. Prostate. 1989;15(2):171-5. [2798234 ]
  16. Cutolo M, Seriolo B, Villaggio B, Pizzorni C, Craviotto C, Sulli A: Androgens and estrogens modulate the immune and inflammatory responses in rheumatoid arthritis. Ann N Y Acad Sci. 2002 Jun;966:131-42. [12114267 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Zinc ion binding
Specific Function:
Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3.
Gene Name:
AR
Uniprot ID:
P10275
Molecular Weight:
98987.9 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.81 uMATG_AR_TRANSAttagene
AC500.000566 uMNVS_NR_hARNovascreen
AC500.0024 uMOT_AR_ARSRC1_0480Odyssey Thera
AC500.00164 uMOT_AR_ARSRC1_0960Odyssey Thera
AC500.00256 uMTox21_AR_BLA_Agonist_ratioTox21/NCGC
AC500.000568 uMTox21_AR_LUC_MDAKB2_AgonistTox21/NCGC
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Zinc ion binding
Specific Function:
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
Gene Name:
ESR1
Uniprot ID:
P03372
Molecular Weight:
66215.45 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.157 uMACEA_T47D_80hr_PositiveACEA Biosciences
AC506.56 uMATG_ERa_TRANSAttagene
AC502.87 uMATG_ERE_CISAttagene
AC500.205 uMNVS_NR_hERNovascreen
AC504.6 uMOT_ERa_EREGFP_0120Odyssey Thera
AC508.59 uMOT_ERa_EREGFP_0480Odyssey Thera
AC500.618 uMTox21_ERa_BLA_Agonist_ratioTox21/NCGC
AC500.06 uMTox21_ERa_BLA_Antagonist_ratioTox21/NCGC
AC500.0888 uMTox21_ERa_LUC_BG1_AgonistTox21/NCGC
AC500.0186 uMTox21_ERa_LUC_BG1_AntagonistTox21/NCGC
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Oxygen binding
Specific Function:
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Gene Name:
CYP19A1
Uniprot ID:
P11511
Molecular Weight:
57882.48 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.0256 uMTox21_Aromatase_InhibitionTox21/NCGC
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Zinc ion binding
Specific Function:
The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor isoform B (PRB) is involved activation of c-SRC/MAPK signaling on hormone stimulation.Isoform A: inactive in stimulating c-Src/MAPK signaling on hormone stimulation.Isoform 4: Increases mitochondrial membrane potential and cellular respiration upon stimulation by progesterone.
Gene Name:
PGR
Uniprot ID:
P06401
Molecular Weight:
98979.96 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.262 uMNVS_NR_hPRNovascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Zinc ion binding
Specific Function:
Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth. Involved in chromatin remodeling. May play a negative role in adipogenesis through the regulation of lipolytic and antilipogenic genes expression.
Gene Name:
NR3C1
Uniprot ID:
P04150
Molecular Weight:
85658.57 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.79 uMNVS_NR_hGRNovascreen
AC501.99 uMTox21_GR_BLA_Antagonist_ratioTox21/NCGC
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Zinc ion binding
Specific Function:
Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner (PubMed:20074560). Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual.
Gene Name:
ESR2
Uniprot ID:
Q92731
Molecular Weight:
59215.765 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC509.49 uMOT_ER_ERaERb_0480Odyssey Thera
AC507.31 uMOT_ER_ERbERb_0480Odyssey Thera
AC508.77 uMOT_ER_ERbERb_1440Odyssey Thera
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Testosterone dehydrogenase (nad+) activity
Specific Function:
Favors the reduction of estrogens and androgens. Also has 20-alpha-HSD activity. Uses preferentially NADH.
Gene Name:
HSD17B1
Uniprot ID:
P14061
Molecular Weight:
34949.715 Da