Tmic
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Record Information
Version2.0
Creation Date2014-08-29 05:59:33 UTC
Update Date2014-12-24 20:26:43 UTC
Accession NumberT3D4240
Identification
Common NameAndrostenedione
ClassSmall Molecule
DescriptionAndrostenedione is a delta-4 19-carbon steroid that is produced not only in the testis, but also in the ovary and the adrenal cortex. Depending on the tissue type, androstenedione can serve as a precursor to testosterone as well as estrone and estradiol. It is the common precursor of male and female sex hormones. Some androstenedione is also secreted into the plasma, and may be converted in peripheral tissues to testosterone and estrogens. Androstenedione originates either from the conversion of dehydroepiandrosterone or from 17-hydroxyprogesterone. It is further converted to either testosterone or estrone. The production of adrenal androstenedione is governed by ACTH, while production of gonadal androstenedione is under control by gonadotropins.
Compound Type
  • Animal Toxin
  • Ester
  • Food Toxin
  • Industrial/Workplace Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(4)-Androsten-3,17-dione
17-Ketotestosterone
3,17-Dioxoandrost-4-ene
4-Androsten-3,17-dione
4-Androstene-3,17-dione
4-Androstenedione
Androst-4-ene-3,17-dione
Androstendione
D4-Androstene-3,17-dione
Delta4-androstenedione
Fecundin
[4-14C]-androstenedione
[4-14C]androst-4-ene-3,17-dione
Chemical FormulaC19H26O2
Average Molecular Mass286.409 g/mol
Monoisotopic Mass286.193 g/mol
CAS Registry Number63-05-8
IUPAC Name(1S,2R,10R,11S,15S)-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-ene-5,14-dione
Traditional Name(1S,2R,10R,11S,15S)-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-ene-5,14-dione
SMILES[H][C@@]12CCC(=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C
InChI IdentifierInChI=1S/C19H26O2/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/h11,14-16H,3-10H2,1-2H3/t14-,15-,16-,18-,19-/m0/s1
InChI KeyInChIKey=AEMFNILZOJDQLW-QAGGRKNESA-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
  • Oxosteroid
  • 17-oxosteroid
  • 3-oxosteroid
  • 3-oxo-delta-4-steroid
  • Delta-4-steroid
  • Cyclohexenone
  • Cyclic ketone
  • Ketone
  • Organic oxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • 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
  • Kidney
  • Liver
  • Muscle
  • Placenta
  • Prostate
  • Skin
  • Testes
Pathways
NameSMPDB LinkKEGG Link
Androgen and Estrogen MetabolismSMP00068 map00150
17-Beta Hydroxysteroid Dehydrogenase III DeficiencySMP00356 Not Available
Adrenal Hyperplasia Type 3 or Congenital Adrenal Hyperplasia due to 21-hydroxylase DeficiencySMP00373 Not Available
Aromatase deficiencySMP00565 Not Available
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point170 - 173°C
Boiling PointNot Available
Solubility0.0578 mg/mL
LogP2.75
Predicted Properties
PropertyValueSource
Water Solubility0.027 g/LALOGPS
logP2.93ALOGPS
logP3.93ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)19.03ChemAxon
pKa (Strongest Basic)-4.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area34.14 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity83.61 m³·mol⁻¹ChemAxon
Polarizability33.21 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 - GC-MS (Non-derivatized)splash10-004l-5910000000-518e1ad38bcc73325b53View in MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-004l-5910000000-5172e05f9889ee2bfaf4View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-000f-8940000000-f2892fe3b281d44164c8View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-007d-1960000000-167f1765b095da9d603bView in MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-004l-5910000000-518e1ad38bcc73325b53View in MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-004l-5910000000-5172e05f9889ee2bfaf4View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4i-0590000000-502d6b821317a01a1990View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-000i-0090000000-36e848ba16b141eef47bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-052b-9600000000-712954fc35a84c8217deView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-052b-9300000000-f8e9aa16b4b208b69f7bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - EI-B (HITACHI M-80) , Positivesplash10-000f-8940000000-e12025ea2b7808c64b9cView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-052b-6910000000-b616785c86a92f46158eView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-052b-9800000000-73e545a1eb2232d55371View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-00kb-5790000000-735473bc44dd70e29259View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-00kb-5790000000-114675a4457063901f2bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0190000000-0347db9e9578e8d5d6f2View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-05pc-0490000000-d4049441f1c172450dc3View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0uk9-4790000000-355bc0834a6465ecad30View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-0090000000-887b6f223b77c683ef99View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000i-0090000000-9dafdd780cca012f1fb3View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-05mo-2190000000-264074b1eefeed0e3103View in MoNA
MSMass Spectrum (Electron Ionization)splash10-059m-3940000000-9cb32ac21e46afb2829aView in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableView in JSpectraViewer
Toxicity Profile
Route of ExposureEndogenous, ingestion
Mechanism of ToxicityAndrostenedione is converted to testosterone and estrogen, and when taken in sufficient quantities androstenedione can cause unwanted masculinizing and feminizing effects. Androstenedione is considered an androgenic steroid precursor because testosterone is an androgen or male hormone. In males, conversion of androstenedione to testosterone requires the enzyme 17β-hydroxysteroid dehydrogenase. In females, conversion of androstenedione to estrogen (e.g., estrone and estradiol) requires the enzyme aromatase.
MetabolismAndrostenedione originates either from the conversion of dehydroepiandrosterone or from 17-hydroxyprogesterone. It is further converted to either testosterone or estrone. The production of adrenal androstenedione is governed by ACTH, while production of gonadal androstenedione is under control by gonadotropins. In males, conversion of androstenedione to testosterone requires the enzyme 17β-hydroxysteroid dehydrogenase. In females, conversion of androstenedione to estrogen (e.g., estrone and estradiol) requires the enzyme aromatase.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesNot Available
Minimum Risk LevelNot Available
Health EffectsAndrostenedione was legally defined as an anabolic steroid by the FDA in 2004. It poses significant health risks commonly associated with steroids. The side effects for men include breast development, behavioral changes, heart disease, and more. Side effects for women are similar to the side effects from anabolic steroids in that their voices will deepen and they may grow facial hair since both occur from an increase level of testosterone. Another side effect of androstenedione is male pattern baldness. The main psychological side effect of androstenedione is depression. Mood swings are also common. Chronically high levels of androstenedione are associated with male pseudohermaphrodism with gynecomastia, Adrenal Hyperplasia Type 3 and Aromatase deficiency.
SymptomsBreast development (in men), behavioral changes, heart disease, male pattern baldness and depression. Side effects for women include a deepening and they may grow facial hair. In children or fetuses high levels of androstenedione (CAH) can lead to a number of changes. Females with congenital adrenal hyperplasia are born with an enlarged clitoris and normal internal reproductive tract structures. Males have normal genitals at birth. CAH causes abnormal growth for both sexes; patients will be tall as children and short as adults. Females develop male characteristics, and males experience premature sexual development.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01536
HMDB IDHMDB00053
PubChem Compound ID6128
ChEMBL IDCHEMBL274826
ChemSpider ID5898
KEGG IDC00280
UniProt IDNot Available
OMIM ID
ChEBI ID16422
BioCyc IDANDROST4ENE
CTD IDNot Available
Stitch IDNot Available
PDB IDASD
ACToR IDNot Available
Wikipedia LinkAndrostenedione
References
Synthesis Reference

Angela M. H. Brodie, Harry J. Brodie, David A. Marsh, “Ester derivatives of 4-hydroxy-4-androstene-3,17-dione and a method for inhibiting estrogen biosynthesis.” U.S. Patent US4235893, issued October, 1962.

MSDST3D4240.pdf
General References
  1. Berkovitz GD, Guerami A, Brown TR, MacDonald PC, Migeon CJ: Familial gynecomastia with increased extraglandular aromatization of plasma carbon19-steroids. J Clin Invest. 1985 Jun;75(6):1763-9. [3924954 ]
  2. Cutolo M, Sulli A, Capellino S, Villaggio B, Montagna P, Pizzorni C, Paolino S, Seriolo B, Felli L, Straub RH: Anti-TNF and sex hormones. Ann N Y Acad Sci. 2006 Jun;1069:391-400. [16855166 ]
  3. Schwarz S, Pohl P: Steroid hormones and steroid hormone binding globulins in cerebrospinal fluid studied in individuals with intact and with disturbed blood-cerebrospinal fluid barrier. Neuroendocrinology. 1992 Feb;55(2):174-82. [1620285 ]
  4. van Vloten WA, van Haselen CW, van Zuuren EJ, Gerlinger C, Heithecker R: The effect of 2 combined oral Contraceptives containing either drospirenone or cyproterone acetate on acne and seborrhea. Cutis. 2002 Apr;69(4 Suppl):2-15. [12096825 ]
  5. Jasuja R, Ramaraj P, Mac RP, Singh AB, Storer TW, Artaza J, Miller A, Singh R, Taylor WE, Lee ML, Davidson T, Sinha-Hikim I, Gonzalez-Cadavid N, Bhasin S: Delta-4-androstene-3,17-dione binds androgen receptor, promotes myogenesis in vitro, and increases serum testosterone levels, fat-free mass, and muscle strength in hypogonadal men. J Clin Endocrinol Metab. 2005 Feb;90(2):855-63. Epub 2004 Nov 2. [15522925 ]
  6. Egloff M, Savoure N, Tardivel-Lacombe J, Massart C, Nicol M, Degrelle H: Influence of sex hormone binding globulin and serum albumin on the conversion of androstenedione to testosterone by human erythrocytes. Acta Endocrinol (Copenh). 1981 Jan;96(1):136-40. [7192922 ]
  7. Zarrilli S, Lombardi G, Paesano L, Di Somma C, Colao A, Mirone V, De Rosa M: Hormonal and seminal evaluation of Leydig cell tumour patients before and after orchiectomy. Andrologia. 2000 May;32(3):147-54. [10863969 ]
  8. Heikkila R, Aho K, Heliovaara M, Hakama M, Marniemi J, Reunanen A, Knekt P: Serum testosterone and sex hormone-binding globulin concentrations and the risk of prostate carcinoma: a longitudinal study. Cancer. 1999 Jul 15;86(2):312-5. [10421267 ]
  9. Schlaghecke R, Kley HK, Kruskemper HL: The measurement of 4-androstene-3, 11, 17-trione (11-oxo-androstenedione) by radioimmunoassay in human plasma. Steroids. 1984 Jul;44(1):23-33. [6100340 ]
  10. King DS, Sharp RL, Vukovich MD, Brown GA, Reifenrath TA, Uhl NL, Parsons KA: Effect of oral androstenedione on serum testosterone and adaptations to resistance training in young men: a randomized controlled trial. JAMA. 1999 Jun 2;281(21):2020-8. [10359391 ]
  11. Johansson A, Henriksson A, Olofsson BO, Olsson T: Adrenal steroid dysregulation in dystrophia myotonica. J Intern Med. 1999 Apr;245(4):345-51. [10356596 ]
  12. Atkinson G, Campbell DJ, Cawood ML, Oakey RE: Steroids in human intrauterine fluids of early pregnancy. Clin Endocrinol (Oxf). 1996 Apr;44(4):435-40. [8706310 ]
  13. Zarrilli S, Paesano L, Mirone V, Finelli L, De Rosa M: [Evaluation of seminal and hormonal parameters in idiopathic varicocele before and after surgical intervention]. Chir Ital. 1998 Mar-Aug;50(2-4):21-8. [11762080 ]
  14. Berria R, Gastaldelli A, Lucidi S, Belfort R, De Filippis E, Easton C, Brytzki R, Cusi K, Jovanovic L, DeFronzo R: Reduction in hematocrit level after pioglitazone treatment is correlated with decreased plasma free testosterone level, not hemodilution, in women with polycystic ovary syndrome. Clin Pharmacol Ther. 2006 Aug;80(2):105-14. Epub 2006 Jun 30. [16890572 ]
  15. Thomson S, Wallace AM, Cook B: A 125I-radioimmunoassay for measuring androstenedione in serum and in blood-spot samples from neonates. Clin Chem. 1989 Aug;35(8):1706-12. [2758640 ]
  16. Riikonen RS: How do cryptogenic and symptomatic infantile spasms differ? Review of biochemical studies in Finnish patients. J Child Neurol. 1996 Sep;11(5):383-8. [8877606 ]
  17. Azurmendi A, Braza F, Sorozabal A, Garcia A, Braza P, Carreras MR, Munoz JM, Cardas J, Sanchez-Martin JR: Cognitive abilities, androgen levels, and body mass index in 5-year-old children. Horm Behav. 2005 Aug;48(2):187-95. [15878571 ]
  18. Schairer C, Hill D, Sturgeon SR, Fears T, Mies C, Ziegler RG, Hoover RN, Sherman ME: Serum concentrations of estrogens, sex hormone binding globulin, and androgens and risk of breast hyperplasia in postmenopausal women. Cancer Epidemiol Biomarkers Prev. 2005 Jul;14(7):1660-5. [16030098 ]
  19. Feldman PS, Kovacs K, Horvath E, Adelson GL: Malignant Leydig cell tumor: clinical, histologic and electron microscopic features. Cancer. 1982 Feb 15;49(4):714-21. [7055782 ]
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
AC501.98 uMATG_AR_TRANSAttagene
AC500.10 uMNVS_NR_hARNovascreen
AC500.39 uMOT_AR_ARSRC1_0480Odyssey Thera
AC500.28 uMOT_AR_ARSRC1_0960Odyssey Thera
AC500.13 uMTox21_AR_BLA_Agonist_ratioTox21/NCGC
AC500.02 uMTox21_AR_LUC_MDAKB2_AgonistTox21/NCGC
References
  1. Ma R, Cotton B, Lichtensteiger W, Schlumpf M: UV filters with antagonistic action at androgen receptors in the MDA-kb2 cell transcriptional-activation assay. Toxicol Sci. 2003 Jul;74(1):43-50. Epub 2003 May 2. [12730620 ]
  2. Chen F, Knecht K, Leu C, Rutledge SJ, Scafonas A, Gambone C, Vogel R, Zhang H, Kasparcova V, Bai C, Harada S, Schmidt A, Reszka A, Freedman L: Partial agonist/antagonist properties of androstenedione and 4-androsten-3beta,17beta-diol. J Steroid Biochem Mol Biol. 2004 Aug;91(4-5):247-57. [15336702 ]
  3. Hodgson MC, Astapova I, Hollenberg AN, Balk SP: Activity of androgen receptor antagonist bicalutamide in prostate cancer cells is independent of NCoR and SMRT corepressors. Cancer Res. 2007 Sep 1;67(17):8388-95. [17804755 ]
  4. Teng C, Goodwin B, Shockley K, Xia M, Huang R, Norris J, Merrick BA, Jetten AM, Austin CP, Tice RR: Bisphenol A affects androgen receptor function via multiple mechanisms. Chem Biol Interact. 2013 May 25;203(3):556-64. doi: 10.1016/j.cbi.2013.03.013. Epub 2013 Apr 4. [23562765 ]
  5. 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 17-beta-dehydrogenase (nadp+) activity
Specific Function:
Favors the reduction of androstenedione to testosterone. Uses NADPH while the two other EDH17B enzymes use NADH.
Gene Name:
HSD17B3
Uniprot ID:
P37058
Molecular Weight:
34515.345 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.489 uMNot AvailableBindingDB 91713
IC500.65 uMNot AvailableBindingDB 91713
IC500.758 uMNot AvailableBindingDB 91713
References
  1. Maltais R, Luu-The V, Poirier D: Synthesis and optimization of a new family of type 3 17 beta-hydroxysteroid dehydrogenase inhibitors by parallel liquid-phase chemistry. J Med Chem. 2002 Jan 31;45(3):640-53. [11806715 ]
  2. Ngatcha BT, Luu-The V, Poirier D: Androsterone 3beta-substituted derivatives as inhibitors of type 3 17beta-hydroxysteroid dehydrogenase. Bioorg Med Chem Lett. 2000 Nov 20;10(22):2533-6. [11086723 ]
  3. Tchedam Ngatcha B, Luu-The V, Labrie F, Poirier D: Androsterone 3alpha-ether-3beta-substituted and androsterone 3beta-substituted derivatives as inhibitors of type 3 17beta-hydroxysteroid dehydrogenase: chemical synthesis and structure-activity relationship. J Med Chem. 2005 Aug 11;48(16):5257-68. [16078844 ]
General Function:
Trans-1,2-dihydrobenzene-1,2-diol dehydrogenase activity
Specific Function:
Catalyzes the conversion of aldehydes and ketones to alcohols. Catalyzes the reduction of prostaglandin (PG) D2, PGH2 and phenanthrenequinone (PQ) and the oxidation of 9-alpha,11-beta-PGF2 to PGD2. Functions as a bi-directional 3-alpha-, 17-beta- and 20-alpha HSD. Can interconvert active androgens, estrogens and progestins with their cognate inactive metabolites. Preferentially transforms androstenedione (4-dione) to testosterone.
Gene Name:
AKR1C3
Uniprot ID:
P42330
Molecular Weight:
36852.89 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
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
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
General Function:
Steroid delta-isomerase activity
Specific Function:
3-beta-HSD is a bifunctional enzyme, that catalyzes the oxidative conversion of Delta(5)-ene-3-beta-hydroxy steroid, and the oxidative conversion of ketosteroids. The 3-beta-HSD enzymatic system plays a crucial role in the biosynthesis of all classes of hormonal steroids. Efficiently catalyzes the transformation of pregnenolone to progesterone, 17-alpha-hydroxypregnenolone to 17-alpha-hydroxyprogesterone, DHEA to 4-androstenedione, dihydrotestosterone to 5-alpha-androstane-3 beta,17 beta-diol, dehydroepiandrosterone to androstenedione and 5-alpha-androstan-3 beta,17 beta-diol to 5-alpha-dihydrotestosterone.
Gene Name:
HSD3B1
Uniprot ID:
P14060
Molecular Weight:
42251.25 Da
References
  1. Ishii-Ohba H, Inano H, Tamaoki B: Purification and properties of testicular 3 beta-hydroxy-5-ene-steroid dehydrogenase and 5-ene-4-ene isomerase. J Steroid Biochem. 1986 Oct;25(4):555-60. [2945972 ]
General Function:
Androgen binding
Specific Function:
Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone, and 17-beta-estradiol. Regulates the plasma metabolic clearance rate of steroid hormones by controlling their plasma concentration.
Gene Name:
SHBG
Uniprot ID:
P04278
Molecular Weight:
43778.755 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Dissociation0.035 uMNot AvailableBindingDB 91713
References
  1. Cherkasov A, Ban F, Santos-Filho O, Thorsteinson N, Fallahi M, Hammond GL: An updated steroid benchmark set and its application in the discovery of novel nanomolar ligands of sex hormone-binding globulin. J Med Chem. 2008 Apr 10;51(7):2047-56. doi: 10.1021/jm7011485. Epub 2008 Mar 11. [18330978 ]
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
AC500.09 uMATG_ERa_TRANSAttagene
AC500.09 uMATG_ERE_CISAttagene
AC500.23 uMTox21_ERa_LUC_BG1_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:
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
AC501.40 uMNVS_ADME_hCYP19A1Novascreen
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:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC505.06 uMNVS_ADME_hCYP2C19Novascreen
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 receptor. Binds preferentially to double-stranded oligonucleotide direct repeats having the consensus half-site sequence 5'-AGGTCA-3' and 4-nt spacing (DR-4). Regulates cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8; DLDLR and LRP8. Interplays functionally with RORA for the regulation of genes involved in liver metabolism (By similarity). Exhibits a ligand-dependent transcriptional activation activity (PubMed:25661920).
Gene Name:
NR1H2
Uniprot ID:
P55055
Molecular Weight:
50973.375 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC508.02 uMATG_LXRb_TRANSAttagene
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
AC508.11 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 ]