Androstenedione
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Basic Info
| Common Name | Androstenedione(F05296) |
| 2D Structure | |
| Description | Androstenedione 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. |
| FRCD ID | F05296 |
| CAS Number | 63-05-8 |
| PubChem CID | 6128 |
| Formula | C19H26O2 |
| IUPAC Name | (8R,9S,10R,13S,14S)-10,13-dimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthrene-3,17-dione |
| InChI Key | AEMFNILZOJDQLW-QAGGRKNESA-N |
| InChI | InChI=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 |
| Canonical SMILES | CC12CCC(=O)C=C1CCC3C2CCC4(C3CCC4=O)C |
| Isomeric SMILES | C[C@]12CCC(=O)C=C1CC[C@@H]3[C@@H]2CC[C@]4([C@H]3CCC4=O)C |
| Wikipedia | Androstenedione |
| Synonyms |
delta-4-Androstenedione
androstenedione
4-Androstene-3,17-dione
Androst-4-ene-3,17-dione
63-05-8
4-Androstenedione
Androtex
3,17-Dioxoandrost-4-ene
SKF 2170
Fecundin
|
| Classifies |
Animal Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Lipids and lipid-like molecules |
| Class | Steroids and steroid derivatives |
| Subclass | Androstane steroids |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Androgens and derivatives |
| Alternative Parents | |
| Molecular Framework | Aliphatic homopolycyclic compounds |
| 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 |
| Description | This 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 Name | Property Value |
|---|---|
| Molecular Weight | 286.415 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 2 |
| Rotatable Bond Count | 0 |
| Complexity | 546 |
| Monoisotopic Mass | 286.193 |
| Exact Mass | 286.193 |
| XLogP | 2.7 |
| Formal Charge | 0 |
| Heavy Atom Count | 21 |
| Defined Atom Stereocenter Count | 5 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.9793 |
| Human Intestinal Absorption | HIA+ | 1.0000 |
| Caco-2 Permeability | Caco2+ | 0.8011 |
| P-glycoprotein Substrate | Substrate | 0.5526 |
| P-glycoprotein Inhibitor | Inhibitor | 0.8564 |
| Non-inhibitor | 0.6615 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.6632 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.6953 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8548 |
| CYP450 2D6 Substrate | Non-substrate | 0.9131 |
| CYP450 3A4 Substrate | Substrate | 0.7193 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.9046 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.9387 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9386 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.8138 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.8483 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.8067 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.7599 |
| Non-inhibitor | 0.7469 | |
| AMES Toxicity | Non AMES toxic | 0.9508 |
| Carcinogens | Non-carcinogens | 0.9313 |
| Fish Toxicity | High FHMT | 0.9773 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.8648 |
| Honey Bee Toxicity | High HBT | 0.8182 |
| Biodegradation | Not ready biodegradable | 0.9343 |
| Acute Oral Toxicity | III | 0.7373 |
| Carcinogenicity (Three-class) | Warning | 0.4588 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -3.7528 | LogS |
| Caco-2 Permeability | 1.7593 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 1.5360 | LD50, mol/kg |
| Fish Toxicity | 0.2662 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.5188 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Contaminants of emerging concern in surface waters in Barbados, West Indies. | Environ Monit Assess | 2017 Nov 14 | 29138943 |
| Relationships between POPs, biometrics and circulating steroids in male polarbears (Ursus maritimus) from Svalbard. | Environ Pollut | 2017 Nov | 28710978 |
| Gossypol inhibits LH-induced steroidogenesis in bovine theca cells. | Anim Sci J | 2017 Jan | 27128796 |
| Effects of butylated hydroxyanisole on the steroidogenesis of rat immature Leydigcells. | Toxicol Mech Methods | 2016 Sep | 27388148 |
| Accelerated follicle growth during the culture of isolated caprine preantralfollicles is detrimental to follicular survival and oocyte meiotic resumption. | Theriogenology | 2016 Oct 1 | 27371972 |
| Equol inhibits growth, induces atresia, and inhibits steroidogenesis of mouseantral follicles in vitro. | Toxicol Appl Pharmacol | 2016 Mar 15 | 26876617 |
| Direct effects of the algal toxin, domoic acid, on ovarian function: Bovine granulosa and theca cells as an in vitro model. | Ecotoxicol Environ Saf | 2015 Mar | 25528487 |
| Disposition and metabolic profile of the weak androgen Dehydroepiandrosterone(DHEA) following administration as part of a nutritional supplement to exercised horses. | Drug Test Anal | 2015 Jan | 25242721 |
| T-2 toxin regulates steroid hormone secretion of rat ovarian granulosa cells through cAMP-PKA pathway. | Toxicol Lett | 2015 Feb 3 | 25542145 |
| Hydroxylated polychlorinated biphenyls decrease circulating steroids in femalepolar bears (Ursus maritimus). | Environ Res | 2015 Apr | 25725300 |
| Experimental model of toxin-induced subclinical mastitis and its effect on disruption of follicular function in cows. | Theriogenology | 2014 Nov | 25212394 |
| High cortisol and cortisone levels are associated with breast milk dioxin concentrations in Vietnamese women. | Eur J Endocrinol | 2014 Jan | 24123093 |
| Peptidoglycan inhibits progesterone and androstenedione production in bovine ovarian theca cells. | Toxicol In Vitro | 2014 Aug | 24727680 |
| Lipopolysaccharide (LPS) inhibits steroid production in theca cells of bovine follicles in vitro: distinct effect of LPS on theca cell function in pre- and post-selection follicles. | J Reprod Dev | 2014 | 24769841 |
| Yolk concentrations of hormones and glucose and egg weight and egg dimensions in unincubated chicken eggs, in relation to egg sex and hen body weight. | Gen Comp Endocrinol | 2013 Jun 15 | 23510857 |
| Estradiol synthesis and release in cultured female rat bone marrow stem cells. | Biomed Res Int | 2013 | 23484106 |
| Molecularly imprinted polymer applied to the selective isolation of urinarysteroid hormones: an efficient tool in the control of natural steroid hormonesabuse in cattle. | J Chromatogr A | 2012 Dec 28 | 23195708 |
| Confirmatory analysis of steroids in muscle using liquid chromatography-tandemmass spectrometry. | Food Addit Contam Part A Chem Anal Control Expo Risk Assess | 2011Apr | 21337239 |
| Immediate and carryover effects of Gram-negative and Gram-positive toxin-induced mastitis on follicular function in dairy cows. | Theriogenology | 2011 Sep 15 | 21705051 |
| Maternal exposure to benzo[b]fluoranthene disturbs reproductive performance in male offspring mice. | Toxicol Lett | 2011 May 30 | 21392559 |
Targets
- 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
- 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:
- 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
References
- 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 ]
- 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
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- 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
- 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
References
- 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
References
- 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
References
- 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:
- 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
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
- 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
- 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:
- 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
- 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 ]
- 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
- 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 ]