Tmic
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Record Information
Version2.0
Creation Date2014-08-29 06:14:17 UTC
Update Date2014-12-24 20:26:45 UTC
Accession NumberT3D4283
Identification
Common NameTestosterone
ClassSmall Molecule
DescriptionTestosterone is the most important androgen in potency and quantity•_Оa steroid sex hormone found in both men and women. Testosterone is synthesized and released by the Leydig cells that lie between the tubules and comprise less than 5% of the total testicular volume. testosterone diffuses into the seminiferous tubules where it is essential for maintaining spermatogenesis. Some binds to an androgen-binding protein (ABP) that is produced by the Sertoli cells and is homologous to the sex-hormone binding globulin that transports testosterone in the general circulation. The ABP carries testosterone in the testicular fluid where it maintains the activity of the accessory sex glands and may also help to retain testosterone within the tubule and bind excess free hormone. Some testosterone is converted to estradiol by Sertoli cell-derived aromatase enzyme. Leydig cell steroidogenesis is controlled primarily by luteinizing hormone with negative feedback of testosterone on the hypothalamic-pituitary axis. The requirement of spermatogenesis for high local concentrations of testosterone means that loss of androgen production is likely to be accompanied by loss of spermatogenesis. Indeed, if testicular androgen production is inhibited by the administration of exogenous androgens then spermatogenesis ceases. This is the basis of using exogenous testosterone as a male contraceptive. testosterone is converted to dihydrotestosterone by 5a-reductase type 2 (EC 1.3.1.22, SRD5A2), the androgen with the highest affinity for the androgen receptor. SRD5A2 deficiency illustrates the importance of dihydrotestosterone for external virilization, as individuals with this condition have normal male internal structures but their external genitalia are of female appearance. There is now clear evidence that the human fetal testis and also the fetal adrenal gland is capable of testosterone biosynthesis during the first trimester. Regardless of the source of androgen production, the target tissue responds by male sexual differentiation of the external genitalia by the end of the first trimester. It is clear that testicular damage may result in loss of testosterone production or the loss of spermatogenesis or both. Loss of androgen production results in hypogonadism, the symptoms of which reflect the functions of testosterone. Male hypogonadism is defined as failure of the testes to produce normal amounts of testosterone, combined with signs and symptoms of androgen deficiency. Systemic testosterone levels fall by about 1% each year in men. Therefore, with increasing longevity and the aging of the population, the number of older men with testosterone deficiency will increase substantially over the next several decades. Serum testosterone levels decrease progressively in aging men, but the rate and magnitude of decrease vary considerably. Approximately 1% of healthy young men have total serum testosterone levels below normal; in contrast, approximately 20% of healthy men over age 60 years have serum testosterone levels below normal. (1, 2). In men, testosterone is produced primarily by the Leydig (interstitial) cells of the testes when stimulated by luteinizing hormone (LH). It functions to stimulate spermatogenesis, promote physical and functional maturation of spermatozoa, maintain accessory organs of the male reproductive tract, support development of secondary sexual characteristics, stimulate growth and metabolism throughout the body and influence brain development by stimulating sexual behaviors and sexual drive. In women, testosterone is produced by the ovaries (25%), adrenals (25%) and via peripheral conversion from androstenedione (50%). Testerone in women functions to maintain libido and general wellbeing. Testosterone exerts a negative feedback mechanism on pituitary release of LH and follicle-stimulating hormone (FSH). Testosterone may be further converted to dihydrotestosterone or estradiol depending on the tissue
Compound Type
  • Androgen
  • Animal Toxin
  • Drug
  • Ester
  • Food Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(+)-testosterone
(+-)-8-iso-testosterone
(+-)-retrotestosterone
(+-)-testosterone
(17b)-17-hydroxy-androst-4-en-3-one
13-Iso-testosterone
17-Hydroxy-10,13-dimethyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-cyclopenta[a]phenanthren-3-one
17-Hydroxy-androst-4-en-3-one
17-Hydroxy-D4-androsten-3-one
17a-Hydroxy-(13a)-androst-4-en-3-one
17a-Hydroxy-13a-androst-4-en-3-one
17a-Hydroxy-14b-androst-4-en-3-one
17a-Hydroxy-androst-4-en-3-one
17b-Hydroxy-(10a)-androst-4-en-3-one
17b-Hydroxy-(13a)-androst-4-en-3-one
17b-Hydroxy-(8a)-androst-4-en-3-one
17b-Hydroxy-(8a,10a)-androst-4-en-3-one
17b-Hydroxy-(9b)-androst-4-en-3-one
17b-Hydroxy-(9b,10a)-androst-4-en-3-one
17b-Hydroxy-13a-androst-4-en-3-one
17b-Hydroxy-8a-androst-4-en-3-one
17b-Hydroxy-androst-4-en-3-on
17b-Hydroxy-androst-4-en-3-one
17b-Hydroxy-D4-androsten-3-one
17b-Hydroxyandrost-4-en-3-one
17b-Hydroxyandrost-4-ene-3-one
17b-Testosterone
17beta-hydroxy-4-androsten-3-one
4-Androsten-17beta-ol-3-one
4-androsten-17β-ol-3-one
4-Androsten-3-one-17b-ol
8-Iso-testosterone
9b,10a-Testosterone
9b-Testosterone
Andriol
Androderm
AndroGel
Androlin
Andronaq
Andronate 100
Andronate 200
Andropatch
Andropository 200
Androst-4-en-17b-ol-3-one
Androst-4-ene-17b-ol-3-one
Andrusol
Andryl 200
Aveed
Axiron
Bio-T-Gel
Cristerona T
D4-Androsten-17b-ol-3-one
Delatestryl
Depo-Testadiol
Depo-Testosterone
Epitestosteron
FORTESTA
Geno-cristaux Gremy
Homosteron
Homosterone
Intrinsa
Livensa
Lumitestosteron
Mertestate
Nebido
Neotestis
Oreton
Orquisteron
Perandren
Percutacrine androgenique
Primotest
Primoteston
Rac-17b-hydroxy-(13a)androst-4-en-3-one
Rac-17b-hydroxy-(8a)-androst-4-en-3-one
Rac-17b-hydroxy-(9b,10a)androst-4-en-3-one
Rac-17b-hydroxy-androst-4-en-3-one
Relibra
Retrotestosterone
Striant
Sustanon
Sustanone
Sustason 250
Synandrol F
Teslen
Testamone 100
Testandrone
Testaqua IM
Testiculosterone
Testim
Testobase
Testoderm
Testoderm TTS
Testogel
Testolent
Testolin
Testopatch
Testopel
Testopel Pellets
Testopropon
Testosteroid
Testosteron
Testosterona
Testostérone
Testosteronum
Testoviron Schering
Testoviron T
Testoxyl
Testrin-P.A
Testro AQ
Testrone
Testryl
Tostrelle
Tostrex
Viatrel
Virormone
Virosterone
Chemical FormulaC19H28O2
Average Molecular Mass288.424 g/mol
Monoisotopic Mass288.209 g/mol
CAS Registry Number58-22-0
IUPAC Name(1S,2R,10R,11S,14R,15S)-14-hydroxy-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-en-5-one
Traditional Name(1S,2R,10R,11S,14R,15S)-14-hydroxy-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-en-5-one
SMILES[H][C@]1(O)CC[C@@]2([H])[C@]3([H])CCC4=CC(=O)CC[C@]4(C)[C@@]3([H])CC[C@]12C
InChI IdentifierInChI=1S/C19H28O2/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/h11,14-17,21H,3-10H2,1-2H3/t14-,15-,16-,17-,18-,19-/m0/s1
InChI KeyInChIKey=MUMGGOZAMZWBJJ-DYKIIFRCSA-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-oxo-delta-4-steroid
  • 3-oxosteroid
  • Hydroxysteroid
  • Oxosteroid
  • 17-hydroxysteroid
  • Delta-4-steroid
  • Cyclohexenone
  • Cyclic alcohol
  • Secondary alcohol
  • Ketone
  • Cyclic ketone
  • Organooxygen compound
  • Alcohol
  • Carbonyl group
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organic oxide
  • 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
  • Brain
  • Gonads
  • Hypothalamus
  • Muscle
  • Sperm
  • Testes
Pathways
NameSMPDB LinkKEGG Link
Androgen and Estrogen MetabolismSMP00068 map00150
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 Point155°C
Boiling PointNot Available
Solubility23.4 mg/L (at 25°C)
LogP3.32
Predicted Properties
PropertyValueSource
Water Solubility0.033 g/LALOGPS
logP2.99ALOGPS
logP3.37ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)19.09ChemAxon
pKa (Strongest Basic)-0.88ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity84.43 m³·mol⁻¹ChemAxon
Polarizability33.93 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)splash10-006t-1940000000-716f44b32e61cf34c7b4View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-006t-1940000000-716f44b32e61cf34c7b4View in MoNA
GC-MSGC-MS Spectrum - GC-MS (1 TMS)splash10-004i-3910000000-d6ace9b7f8aff4dd46d0View in MoNA
GC-MSGC-MS Spectrum - GC-MS (2 TMS)splash10-053u-1920200000-db3504f562c54e6e1bbbView in MoNA
GC-MSGC-MS Spectrum - GC-MS (1 MEOX; 1 TMS)splash10-004l-3910000000-b43cd1ee268a855c8aa0View in MoNA
GC-MSGC-MS Spectrum - GC-MS (1 MEOX; 1 TMS)splash10-004l-3910000000-356ddfa8ddf8e551278dView in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0597-7920000000-dde7fba02fcbcec2d665View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-05fs-4920000000-ccd839134de79f179f9eView in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-00ds-0950000000-c65fc8043083ad93d169View in MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-004i-3910000000-d6ace9b7f8aff4dd46d0View in MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-053u-1920200000-db3504f562c54e6e1bbbView in MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-004l-3910000000-b43cd1ee268a855c8aa0View in MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-004l-3910000000-356ddfa8ddf8e551278dView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-074i-0390000000-09e2a725ebd92c93dc88View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-000t-1119000000-bf66038b9de80f6b8aabView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-000i-0090000000-e1af5f6bcaf571731a2bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-052b-7900000000-581eb9c19ccb29ebac52View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-052b-9300000000-37c235bd069ce0c93813View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , negativesplash10-0690-0190000000-d4814fdc14f2b2818eb2View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , positivesplash10-0fk9-1690000000-b39908a52b06c7853085View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00dr-0190000000-4b469479ef097f60ed90View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00dr-0390000000-8bebba5f70c72e80b630View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0udi-5890000000-46ba5a59d051001f2a63View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-0090000000-3c963477109db1f6b39eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000i-0090000000-87d4a2534cd39e8c54a8View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0abc-1190000000-abbd0808a06f67c1f6fcView in MoNA
MSMass Spectrum (Electron Ionization)splash10-00dv-5940000000-5e22fba0c369374c75dfView in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableView in JSpectraViewer
Toxicity Profile
Route of ExposureEndogenous, Injection
Mechanism of ToxicityTestosterone is considered an anabolic steroid. It plays a key role in the development of male reproductive tissues such as the testis and prostate as well as promoting secondary sexual characteristics such as increased muscle, bone mass, and the growth of body hair. High levels of testosterone can lead to masculinization in females or premature puberty in young boys. Chronically high levels in adults increase the incidence of heart attack, stroke and blood clots by lowering the level of HDL (good cholesterol) and increasing the level of LDL (bad cholesterol). Chronic high use of anabolic steroids (such as testosterone) appears to lead to cardiac myopathy and weakening the left ventricle. The development of breast tissue in males, a condition called gynecomastia (which is usually caused by high levels of circulating estradiol), arises because of increased conversion of testosterone to estradiol by the enzyme aromatase. Reduced sexual function and temporary infertility can also occur in males. The mechanism of testosterone’s action is as follows: Free testosterone is transported into the cytoplasm of target tissue cells, where it can bind to the androgen receptor, or can be reduced to 5α-dihydrotestosterone (DHT) by the cytoplasmic enzyme 5-alpha reductase. DHT binds to the same androgen receptor even more strongly than testosterone, so that its androgenic potency is about 5 times that of testosterone. Once bound, the ligand-receptor complex undergoes a structural change that allows it to move into the cell nucleus and bind directly to specific nucleotide sequences of the chromosomal DNA. The areas of binding are called hormone response elements (HREs), and influence transcriptional activity of certain genes, producing the androgen effects.
MetabolismTestosterone is metabolized to 17-keto steroids through two different pathways. The major active metabolites are estradiol and dihydrotestosterone (DHT). Route of Elimination: About 90% of a dose of testosterone given intramuscularly is excreted in the urine as glucuronic and sulfuric acid conjugates of testosterone and its metabolites; about 6% of a dose is excreted in the feces, mostly in the unconjugated form. Half Life: 10-100 minutes
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesTo be used as hormone replacement or substitution of diminished or absent endogenous testosterone. Use in males: For management of congenital or acquired hypogonadism, hypogonadism associated with HIV infection, and male climacteric (andopause). Use in females: For palliative treatment of androgen-responsive, advanced, inoperable, metastatis (skeletal) carcinoma of the breast in women who are 1-5 years postmenopausal; testosterone esters may be used in combination with estrogens in the management of moderate to severe vasomotor symptoms associated with menopause in women who do not respond to adequately to estrogen therapy alone.
Minimum Risk LevelNot Available
Health EffectsIn women, excess testosterone may cause decreased breast size, a deep voice, increased genital size, irregular periods, oily skin, and unnatural hair growth. In men, excess testosterone may cause aggression, breast tenderness or enlargement, decreased testes size, and urinary urgency. Chronically high levels of testosterone are associated with at least 2 inborn errors of metabolism including: Adrenal Hyperplasia Type 3 and Aromatase deficiency.
SymptomsIn women, testosterone may cause decreased breast size, a deep voice, increased genital size, irregular periods, oily skin, and unnatural hair growth. In men, excess testosterone may cause aggression, premature baldness, breast tenderness or enlargement, decreased testes size, and urinary urgency.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00624
HMDB IDHMDB00234
PubChem Compound ID6013
ChEMBL IDCHEMBL386630
ChemSpider ID5791
KEGG IDC00535
UniProt IDNot Available
OMIM ID
ChEBI ID17347
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDTES
ACToR IDNot Available
Wikipedia LinkTestosterone
References
Synthesis Reference

Merle G. Wovcha, Frederick J. Antosz, John M. Beaton, Alfred B. Garcia, Leo A. Kominek, “Process for preparing 9.alpha.-OH testosterone.” U.S. Patent US4221868, issued November, 1977.

MSDSLink
General References
  1. Kazi M, Geraci SA, Koch CA: Considerations for the diagnosis and treatment of testosterone deficiency in elderly men. Am J Med. 2007 Oct;120(10):835-40. [17904450 ]
  2. Krone N, Hanley NA, Arlt W: Age-specific changes in sex steroid biosynthesis and sex development. Best Pract Res Clin Endocrinol Metab. 2007 Sep;21(3):393-401. [17875487 ]
  3. Freeman ER, Bloom DA, McGuire EJ: A brief history of testosterone. J Urol. 2001 Feb;165(2):371-3. [11176375 ]
  4. Hoberman JM, Yesalis CE: The history of synthetic testosterone. Sci Am. 1995 Feb;272(2):76-81. [7817189 ]
  5. Contraceptive efficacy of testosterone-induced azoospermia in normal men. World Health Organization Task Force on methods for the regulation of male fertility. Lancet. 1990 Oct 20;336(8721):955-9. [1977002 ]
  6. Dean JD, Carnegie C, Rodzvilla J, Smith T: Long-term effects of testim(r) 1% testosterone gel in hypogonadal men. Rev Urol. 2004;6 Suppl 6:S22-9. [16985908 ]
  7. Handelsman DJ: Clinical review: The rationale for banning human chorionic gonadotropin and estrogen blockers in sport. J Clin Endocrinol Metab. 2006 May;91(5):1646-53. Epub 2006 Feb 14. [16478815 ]
  8. Duschek EJ, Gooren LJ, Netelenbos C: Comparison of effects of the rise in serum testosterone by raloxifene and oral testosterone on serum insulin-like growth factor-1 and insulin-like growth factor binding protein-3. Maturitas. 2005 Jul 16;51(3):286-93. [15978972 ]
  9. Schaap LA, Pluijm SM, Smit JH, van Schoor NM, Visser M, Gooren LJ, Lips P: The association of sex hormone levels with poor mobility, low muscle strength and incidence of falls among older men and women. Clin Endocrinol (Oxf). 2005 Aug;63(2):152-60. [16060908 ]
  10. Kim YS, Zhang H, Kim HY: Profiling neurosteroids in cerebrospinal fluids and plasma by gas chromatography/electron capture negative chemical ionization mass spectrometry. Anal Biochem. 2000 Jan 15;277(2):187-95. [10625505 ]
  11. Huang I, Jones J, Khorram O: Human seminal plasma nitric oxide: correlation with sperm morphology and testosterone. Med Sci Monit. 2006 Mar;12(3):CR103-6. Epub 2006 Feb 23. [16501419 ]
  12. Hussein A, Ozgok Y, Ross L, Niederberger C: Clomiphene administration for cases of nonobstructive azoospermia: a multicenter study. J Androl. 2005 Nov-Dec;26(6):787-91; discussion 792-3. [16291975 ]
  13. Ahtiainen JP, Pakarinen A, Alen M, Kraemer WJ, Hakkinen K: Short vs. long rest period between the sets in hypertrophic resistance training: influence on muscle strength, size, and hormonal adaptations in trained men. J Strength Cond Res. 2005 Aug;19(3):572-82. [16095405 ]
  14. Landman AD, Sanford LM, Howland BE, Dawes C, Pritchard ET: Testosterone in human saliva. Experientia. 1976;32(7):940-1. [954994 ]
  15. Knickmeyer RC, Wheelwright S, Taylor K, Raggatt P, Hackett G, Baron-Cohen S: Gender-typed play and amniotic testosterone. Dev Psychol. 2005 May;41(3):517-28. [15910159 ]
  16. Fejes I, Koloszar S, Szollosi J, Zavaczki Z, Pal A: Is semen quality affected by male body fat distribution? Andrologia. 2005 Oct;37(5):155-9. [16266392 ]
  17. Jarow JP, Zirkin BR: The androgen microenvironment of the human testis and hormonal control of spermatogenesis. Ann N Y Acad Sci. 2005 Dec;1061:208-20. [16467270 ]
  18. Rovensky J, Radikova Z, Imrich R, Greguska O, Vigas M, Macho L: Gonadal and adrenal steroid hormones in plasma and synovial fluid of patients with rheumatoid arthritis. Endocr Regul. 2004 Dec;38(4):143-9. [15841793 ]
  19. Klimek M, Pabian W, Tomaszewska B, Kolodziejczyk J: Levels of plasma ACTH in men from infertile couples. Neuro Endocrinol Lett. 2005 Aug;26(4):347-50. [16136011 ]
  20. 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 ]
  21. 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 ]
  22. Shores MM, Matsumoto AM, Sloan KL, Kivlahan DR: Low serum testosterone and mortality in male veterans. Arch Intern Med. 2006 Aug 14-28;166(15):1660-5. [16908801 ]
  23. Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM: Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2006 Jun;91(6):1995-2010. Epub 2006 May 23. [16720669 ]
  24. Archer JS, Love-Geffen TE, Herbst-Damm KL, Swinney DA, Chang JR: Effect of estradiol versus estradiol and testosterone on brain-activation patterns in postmenopausal women. Menopause. 2006 May-Jun;13(3):528-37. [16735951 ]
  25. Jarow JP, Wright WW, Brown TR, Yan X, Zirkin BR: Bioactivity of androgens within the testes and serum of normal men. J Androl. 2005 May-Jun;26(3):343-8. [15867001 ]
  26. Bridger T, MacDonald S, Baltzer F, Rodd C: Randomized placebo-controlled trial of metformin for adolescents with polycystic ovary syndrome. Arch Pediatr Adolesc Med. 2006 Mar;160(3):241-6. [16520442 ]
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
IC500.0027 uMNot AvailableBindingDB 8885
IC500.0039 uMNot AvailableBindingDB 8885
IC500.00457 uMNot AvailableBindingDB 8885
IC500.03 uMNot AvailableBindingDB 8885
References
  1. Small EJ, Ryan CJ: The case for secondary hormonal therapies in the chemotherapy age. J Urol. 2006 Dec;176(6 Pt 2):S66-71. [17084172 ]
  2. Omwancha J, Brown TR: Selective androgen receptor modulators: in pursuit of tissue-selective androgens. Curr Opin Investig Drugs. 2006 Oct;7(10):873-81. [17086931 ]
  3. Petraki CD, Sfikas CP: Histopathological changes induced by therapies in the benign prostate and prostate adenocarcinoma. Histol Histopathol. 2007 Jan;22(1):107-18. [17128417 ]
  4. Maudsley S, Davidson L, Pawson AJ, Freestone SH, Lopez de Maturana R, Thomson AA, Millar RP: Gonadotropin-releasing hormone functionally antagonizes testosterone activation of the human androgen receptor in prostate cells through focal adhesion complexes involving Hic-5. Neuroendocrinology. 2006;84(5):285-300. Epub 2007 Jan 4. [17202804 ]
  5. Lapauw B, Goemaere S, Crabbe P, Kaufman JM, Ruige JB: Is the effect of testosterone on body composition modulated by the androgen receptor gene CAG repeat polymorphism in elderly men? Eur J Endocrinol. 2007 Mar;156(3):395-401. [17322500 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  7. Blizzard TA, Gude C, Morgan JD 2nd, Chan W, Birzin ET, Mojena M, Tudela C, Chen F, Knecht K, Su Q, Kraker B, Mosley RT, Holmes MA, Sharma N, Fitzgerald PM, Rohrer SP, Hammond ML: Androstenediol analogs as ER-beta-selective SERMs. Bioorg Med Chem Lett. 2006 Feb 15;16(4):834-8. Epub 2005 Nov 23. [16309907 ]
  8. Blizzard TA, Gude C, Chan W, Birzin ET, Mojena M, Tudela C, Chen F, Knecht K, Su Q, Kraker B, Holmes MA, Rohrer SP, Hammond ML: Bridged androstenediol analogs as ER-beta selective SERMs. Bioorg Med Chem Lett. 2007 May 15;17(10):2944-8. Epub 2006 Dec 21. [17448656 ]
  9. Blizzard TA, Gude C, Morgan JD 2nd, Chan W, Birzin ET, Mojena M, Tudela C, Chen F, Knecht K, Su Q, Kraker B, Mosley RT, Holmes MA, Rohrer SP, Hammond ML: Androstene-3,5-dienes as ER-beta selective SERMs. Bioorg Med Chem Lett. 2007 Nov 15;17(22):6295-8. Epub 2007 Sep 7. [17890084 ]
  10. Muddana SS, Price AM, MacBride MM, Peterson BR: 11beta-alkyl-Delta9-19-nortestosterone derivatives: high-affinity ligands and potent partial agonists of the androgen receptor. J Med Chem. 2004 Oct 7;47(21):4985-8. [15456242 ]
  11. Poutiainen PK, Oravilahti T, Perakyla M, Palvimo JJ, Ihalainen JA, Laatikainen R, Pulkkinen JT: Design, synthesis, and biological evaluation of nonsteroidal cycloalkane[d]isoxazole-containing androgen receptor modulators. J Med Chem. 2012 Jul 26;55(14):6316-27. doi: 10.1021/jm300233k. Epub 2012 Jul 11. [22746350 ]
  12. Miller CP, Bhaket P, Muthukaman N, Lyttle CR, Shomali M, Gallacher K, Slocum C, Hattersley G: Synthesis of potent, substituted carbazoles as selective androgen receptor modulators (SARMs). Bioorg Med Chem Lett. 2010 Dec 15;20(24):7516-20. doi: 10.1016/j.bmcl.2010.09.140. Epub 2010 Oct 7. [21036041 ]
  13. Kizu R, Okamura K, Toriba A, Mizokami A, Burnstein KL, Klinge CM, Hayakawa K: Antiandrogenic activities of diesel exhaust particle extracts in PC3/AR human prostate carcinoma cells. Toxicol Sci. 2003 Dec;76(2):299-309. Epub 2003 Sep 11. [12970580 ]
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
IC50>10 uMNot AvailableBindingDB 8885
References
  1. Blizzard TA, Gude C, Morgan JD 2nd, Chan W, Birzin ET, Mojena M, Tudela C, Chen F, Knecht K, Su Q, Kraker B, Mosley RT, Holmes MA, Sharma N, Fitzgerald PM, Rohrer SP, Hammond ML: Androstenediol analogs as ER-beta-selective SERMs. Bioorg Med Chem Lett. 2006 Feb 15;16(4):834-8. Epub 2005 Nov 23. [16309907 ]
  2. Blizzard TA, Gude C, Chan W, Birzin ET, Mojena M, Tudela C, Chen F, Knecht K, Su Q, Kraker B, Holmes MA, Rohrer SP, Hammond ML: Bridged androstenediol analogs as ER-beta selective SERMs. Bioorg Med Chem Lett. 2007 May 15;17(10):2944-8. Epub 2006 Dec 21. [17448656 ]
  3. Blizzard TA, Gude C, Morgan JD 2nd, Chan W, Birzin ET, Mojena M, Tudela C, Chen F, Knecht K, Su Q, Kraker B, Mosley RT, Holmes MA, Rohrer SP, Hammond ML: Androstene-3,5-dienes as ER-beta selective SERMs. Bioorg Med Chem Lett. 2007 Nov 15;17(22):6295-8. Epub 2007 Sep 7. [17890084 ]
  4. Dang Z: Comparison of relative binding affinities to fish and mammalian estrogen receptors: the regulatory implications. Toxicol Lett. 2010 Feb 15;192(3):298-315. doi: 10.1016/j.toxlet.2009.11.004. Epub 2009 Nov 12. [19913605 ]
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
IC50>10 uMNot AvailableBindingDB 8885
References
  1. Blizzard TA, Gude C, Morgan JD 2nd, Chan W, Birzin ET, Mojena M, Tudela C, Chen F, Knecht K, Su Q, Kraker B, Mosley RT, Holmes MA, Sharma N, Fitzgerald PM, Rohrer SP, Hammond ML: Androstenediol analogs as ER-beta-selective SERMs. Bioorg Med Chem Lett. 2006 Feb 15;16(4):834-8. Epub 2005 Nov 23. [16309907 ]
  2. Blizzard TA, Gude C, Chan W, Birzin ET, Mojena M, Tudela C, Chen F, Knecht K, Su Q, Kraker B, Holmes MA, Rohrer SP, Hammond ML: Bridged androstenediol analogs as ER-beta selective SERMs. Bioorg Med Chem Lett. 2007 May 15;17(10):2944-8. Epub 2006 Dec 21. [17448656 ]
  3. Kojima H, Iida M, Katsura E, Kanetoshi A, Hori Y, Kobayashi K: Effects of a diphenyl ether-type herbicide, chlornitrofen, and its amino derivative on androgen and estrogen receptor activities. Environ Health Perspect. 2003 Apr;111(4):497-502. [12676605 ]
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
IC500.014 uMNot AvailableBindingDB 8885
Dissociation0.000631 uMNot AvailableBindingDB 8885
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 ]
  2. Cherkasov A, Ban F, Li Y, Fallahi M, Hammond GL: Progressive docking: a hybrid QSAR/docking approach for accelerating in silico high throughput screening. J Med Chem. 2006 Dec 14;49(25):7466-78. [17149875 ]
General Function:
Transmembrane signaling receptor activity
Specific Function:
Catalyzes the conversion of Delta(8)-sterols to their corresponding Delta(7)-isomers.
Gene Name:
EBP
Uniprot ID:
Q15125
Molecular Weight:
26352.615 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory>100 uMNot AvailableBindingDB 8885
References
  1. Laggner C, Schieferer C, Fiechtner B, Poles G, Hoffmann RD, Glossmann H, Langer T, Moebius FF: Discovery of high-affinity ligands of sigma1 receptor, ERG2, and emopamil binding protein by pharmacophore modeling and virtual screening. J Med Chem. 2005 Jul 28;48(15):4754-64. [16033255 ]
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
Inhibitory0.6 uMNot AvailableBindingDB 8885
References
  1. Foster AB, Jarman M, Leung CS, Rowlands MG, Taylor GN: Analogues of aminoglutethimide: selective inhibition of cholesterol side-chain cleavage. J Med Chem. 1983 Jan;26(1):50-4. [6827528 ]
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide (PubMed:11159812). Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro (PubMed:21576599).
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5010 uMNot AvailableBindingDB 8885
References
  1. Chougnet A, Stoessel C, Woggon WD: Design and synthesis of a new fluorescent probe for cytochrome P450 3A4 (CYP 3A4). Bioorg Med Chem Lett. 2003 Nov 3;13(21):3643-5. [14552748 ]
General Function:
Sterol 14-demethylase activity
Specific Function:
Catalyzes C14-demethylation of lanosterol; it transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol.
Gene Name:
CYP51A1
Uniprot ID:
Q16850
Molecular Weight:
56805.26 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5050 uMNot AvailableBindingDB 8885
References
  1. Ekins S, Mankowski DC, Hoover DJ, Lawton MP, Treadway JL, Harwood HJ Jr: Three-dimensional quantitative structure-activity relationship analysis of human CYP51 inhibitors. Drug Metab Dispos. 2007 Mar;35(3):493-500. Epub 2006 Dec 28. [17194716 ]
General Function:
Zinc ion binding
Specific Function:
Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion and water transport and thus raise extracellular fluid volume and blood pressure and lower potassium levels.
Gene Name:
NR3C2
Uniprot ID:
P08235
Molecular Weight:
107066.575 Da
References
  1. Takeda AN, Pinon GM, Bens M, Fagart J, Rafestin-Oblin ME, Vandewalle A: The synthetic androgen methyltrienolone (r1881) acts as a potent antagonist of the mineralocorticoid receptor. Mol Pharmacol. 2007 Feb;71(2):473-82. Epub 2006 Nov 14. [17105867 ]
General Function:
Opioid receptor activity
Specific Function:
Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma membrane. Involved in the regulation of different receptors it plays a role in BDNF signaling and EGF signaling. Also regulates ion channels like the potassium channel and could modulate neurotransmitter release. Plays a role in calcium signaling through modulation together with ANK2 of the ITP3R-dependent calcium efflux at the endoplasmic reticulum. Plays a role in several other cell functions including proliferation, survival and death. Originally identified for its ability to bind various psychoactive drugs it is involved in learning processes, memory and mood alteration (PubMed:16472803, PubMed:9341151). Necessary for proper mitochondrial axonal transport in motor neurons, in particular the retrograde movement of mitochondria (By similarity).
Gene Name:
SIGMAR1
Uniprot ID:
Q99720
Molecular Weight:
25127.52 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory1.2 uMNot AvailableBindingDB 8885
References
  1. Laggner C, Schieferer C, Fiechtner B, Poles G, Hoffmann RD, Glossmann H, Langer T, Moebius FF: Discovery of high-affinity ligands of sigma1 receptor, ERG2, and emopamil binding protein by pharmacophore modeling and virtual screening. J Med Chem. 2005 Jul 28;48(15):4754-64. [16033255 ]