Basic Info

Common NameTestosterone(F05320)
2D Structure
Description

Testosterone 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. (A3376, A3377). 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

FRCD IDF05320
CAS Number58-22-0
PubChem CID6013
FormulaC19H28O2
IUPAC Name

(8R,9S,10R,13S,14S,17S)-17-hydroxy-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one

InChI Key

MUMGGOZAMZWBJJ-DYKIIFRCSA-N

InChI

InChI=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

Canonical SMILES

CC12CCC3C(C1CCC2O)CCC4=CC(=O)CCC34C

Isomeric SMILES

C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@@H]2O)CCC4=CC(=O)CC[C@]34C

WikipediaTestosterone
Synonyms
        
            Mertestate
        
            testosterone
        
            58-22-0
        
            Testosteron
        
            Androderm
        
            Sustanon
        
            Testoderm
        
            Virosterone
        
            Androlin
        
            Oreton
        
Classifies
                

                  
                    Animal Toxin
                  

                
        
Update DateNov 13, 2018 17:07

Chemical Taxonomy

KingdomOrganic compounds
SuperclassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
SubclassAndrostane steroids
Intermediate Tree NodesNot available
Direct ParentAndrogens and derivatives
Alternative Parents
Molecular FrameworkAliphatic homopolycyclic compounds
SubstituentsAndrogen-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
DescriptionThis compound 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.

Properties

Property NameProperty Value
Molecular Weight288.431
Hydrogen Bond Donor Count1
Hydrogen Bond Acceptor Count2
Rotatable Bond Count0
Complexity508
Monoisotopic Mass288.209
Exact Mass288.209
XLogP3.3
Formal Charge0
Heavy Atom Count21
Defined Atom Stereocenter Count6
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Isotope Atom Count0
Covalently-Bonded Unit Count1

ADMET

Model Result Probability
Absorption
Blood-Brain BarrierBBB+0.9730
Human Intestinal AbsorptionHIA+1.0000
Caco-2 PermeabilityCaco2+0.8984
P-glycoprotein SubstrateSubstrate0.6498
P-glycoprotein InhibitorInhibitor0.5489
Non-inhibitor0.8923
Renal Organic Cation TransporterNon-inhibitor0.7324
Distribution
Subcellular localizationMitochondria0.7307
Metabolism
CYP450 2C9 SubstrateNon-substrate0.8167
CYP450 2D6 SubstrateNon-substrate0.9116
CYP450 3A4 SubstrateSubstrate0.7739
CYP450 1A2 InhibitorNon-inhibitor0.9005
CYP450 2C9 InhibitorNon-inhibitor0.9500
CYP450 2D6 InhibitorNon-inhibitor0.9452
CYP450 2C19 InhibitorNon-inhibitor0.6668
CYP450 3A4 InhibitorNon-inhibitor0.8812
CYP Inhibitory PromiscuityLow CYP Inhibitory Promiscuity0.8683
Excretion
Toxicity
Human Ether-a-go-go-Related Gene InhibitionWeak inhibitor0.8938
Non-inhibitor0.7163
AMES ToxicityNon AMES toxic0.9382
CarcinogensNon-carcinogens0.9483
Fish ToxicityHigh FHMT0.9843
Tetrahymena Pyriformis ToxicityHigh TPT0.9455
Honey Bee ToxicityHigh HBT0.8401
BiodegradationNot ready biodegradable0.9174
Acute Oral ToxicityIII0.5718
Carcinogenicity (Three-class)Warning0.4896

Model Value Unit
Absorption
Aqueous solubility-4.0828LogS
Caco-2 Permeability1.9335LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity1.6259LD50, mol/kg
Fish Toxicity0.5970pLC50, mg/L
Tetrahymena Pyriformis Toxicity0.6246pIGC50, ug/L

References

TitleJournalDatePubmed ID
Evaluation of FSH, LH, testosterone levels and semen parameters in male boron workers under extreme exposure conditions.Arch Toxicol2018 Oct30143848
Encapsulation of cinnamon essential oil in whey protein enhances the protective effect against single or combined sub-chronic toxicity of fumonisin B<sub>1</sub> and/or aflatoxin B<sub>1</sub> in rats.Environ Sci Pollut Res Int2018 Oct30112645
Bisphenol A and its analogs bisphenol B, bisphenol F, and bisphenol S: Comparative in vitro and in vivo studies on the sperms and testicular tissues of rats.Chemosphere2018 Oct29940534
Impact of low-dose chronic exposure to bisphenol A and its analogue bisphenol B, bisphenol F and bisphenol S on hypothalamo-pituitary-testicular activities in adult rats: A focus on the possible hormonal mode of action.Food Chem Toxicol2018 Nov30120946
Chlorinated insecticides (toxaphene and endrin) affect oxytocin, testosterone,oestradiol and prostaglandin secretion from ovarian and uterine cells as well as myometrial contractions in cow in vitro.Chemosphere2018 May29425943
Prenatal exposure to zearalenone disrupts reproductive potential and development via hormone-related genes in male rats.Food Chem Toxicol2018 Jun29627501
Male Hatano low-avoidance rats show more active sexual behavior with lower plasmatestosterone than high-avoidance rats.J Vet Med Sci2018 Jul 1829848887
Ameliorative effect of ginseng extract on phthalate and bisphenol A reprotoxicity during pregnancy in rats.Environ Sci Pollut Res Int2018 Jul29777495
Egg deposition of maternal testosterone is primarily controlled by thepreovulatory peak of luteinizing hormone in Japanese quail.Gen Comp Endocrinol2018 Jan 1528495270
The effect of bisphenol A on testicular steroidogenesis and its amelioration by quercetin: an <i>in vivo</i> and <i>in silico</i> approach.Toxicol Res (Camb)2018 Jan 130090559
Prenatal exposure to di(2-ethylhexyl) phthalate disrupts ovarian function in atransgenerational manner in female mice.Biol Reprod2018 Jan 129165555
Combined effects of simultaneous exposure to six phthalates and emulsifier glycerol monosterate on male reproductive system in rats.Toxicol Appl Pharmacol2018 Feb 1529366639
Prenatal dioxin exposure estimated from dioxins in breast milk and sex hormone levels in umbilical cord blood in Vietnamese newborn infants.Sci Total Environ2018 Feb 1529751436
Urinary Cadmium Excretion Is Associated With Increased Synthesis of Cortico- and Sex Steroids in a Population Study.J Clin Endocrinol Metab2018 Feb 129077874
Reproductive and endocrine-disrupting toxicity of Microcystis aeruginosa in female zebrafish.Chemosphere2018 Feb29112878
Cyanidin-3-O-glucoside promotes the biosynthesis of progesterone through theprotection of mitochondrial function in Pb-exposed rat leydig cells.Food Chem Toxicol2018 Feb29030260
Effects of folic acid on testicular toxicity induced by bisphenol-A in male Wistar rats.Biotech Histochem2018 Aug 630079777
Accumulation of steroid hormones in the eggshells of Japanese quail (Coturnixcoturnix japonica).Gen Comp Endocrinol2018 Apr 129174486
The anti-estrogenicity of chronic exposure to semicarbazide in female Japaneseflounders (Paralichthys olivaceus), and its potential mechanisms.Mar Pollut Bull2018 Apr29100632
Protective effect of Nigella sativa oil against acetamiprid induced reproductive toxicity in male rats.Drug Chem Toxicol2018 Apr28669218

Targets

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
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:
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
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:
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
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:
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
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:
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
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
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
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 ]
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:
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
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 ]
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
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:
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
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 ]