Estrogen metabolism (WP697)
Homo sapiens
Estrogens are metabolized via hydroxylation by cytochrome P450 enzymes such as CYP1A1 and CYP3A4 and via conjugation by estrogen sulfotransferases (sulfation) and UDP-glucuronyltransferases (glucuronidation). In addition, estradiol is dehydrogenated by 17β-Hydroxysteroid dehydrogenase into the much less potent estrogen estrone. These reactions occur primarily in the liver, but also in other tissues. Description source: [https://en.wikipedia.org/wiki/Estrogen#Metabolism Wikipedia]. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP697 CPTAC Assay Portal]
Authors
Pieter Giesbertz , Alex Pico , Martina Summer-Kutmon , Zahra Roudbari , Egon Willighagen , Denise Slenter , Kristina Hanspers , and Eric WeitzActivity
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Cited In
- Genetic Variation and Hot Flashes: A Systematic Review (2020).
- Human Monocytes Exposed to SARS-CoV-2 Display Features of Innate Immune Memory Producing High Levels of CXCL10 upon Restimulation (2023).
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Organisms
Homo sapiensCommunities
Annotations
Pathway Ontology
C18-steroid hormone biosynthetic pathway steroid hormone biosynthetic pathway| Label | Type | Compact URI | Comment |
|---|---|---|---|
| 2-Hydroxyestrone | Metabolite | hmdb:HMDB0000343 | |
| Estrone | Metabolite | hmdb:HMDB0000145 | |
| 4-hydroxyestradiol | Metabolite | pubchem.compound:5282360 | |
| 2-Methoxyestradiol-3-glucuronide | Metabolite | hmdb:HMDB0006765 | |
| 2-Hydroxyestradiol | Metabolite | hmdb:HMDB0000338 | |
| Estradiol sulfate | Metabolite | pubchem.compound:66416 | |
| Estrone sulfate | Metabolite | hmdb:HMDB0001425 | |
| Oxygen | Metabolite | hmdb:HMDB0001377 | |
| ESTRADIOL | Metabolite | chebi:23965 | |
| 4-hydroxyestrone | Metabolite | pubchem.compound:9971251 | |
| Estrone-2,3-quinone | Metabolite | pubchem.compound:148381 | |
| 16a-Hydroxyestrone | Metabolite | hmdb:HMDB0000335 | |
| 2-Methoxyestrone 3-glucuronide | Metabolite | hmdb:HMDB0004482 | |
| 4-hydroxyestrone-3-glucuronide | Metabolite | chebi:136969 | |
| Estradiol-3-glucuronide | Metabolite | hmdb:HMDB0006224 | |
| Superoxide | Metabolite | hmdb:HMDB0002168 | |
| 4-Methoxyestrone-3-glucuronide | Metabolite | chebi:137965 | |
| 2-Methoxyestradiol | Metabolite | hmdb:HMDB0000405 | |
| Estradiol-3,4-quinone | Metabolite | hmdb:HMDB0060085 | |
| Estradiol-17-glucuronide | Metabolite | pubchem.compound:5281887 | |
| Estrone-17-glucuronide | Metabolite | hmdb:HMDB0004483 | |
| 4-hydroxy-estradiol-4-glucuronide | Metabolite | cas:90746-94-4 | |
| Estradiol-2,3-quinone | Metabolite | hmdb:HMDB0060084 | |
| 4-Methoxyestradiol | Metabolite | hmdb:HMDB0000405 | |
| Estrone-3-glucuronide | Metabolite | hmdb:HMDB0004483 | |
| 2-Methoxyestrone | Metabolite | hmdb:HMDB0000010 | |
| 4-Methoxyestrone | Metabolite | pubchem.compound:194066 | |
| Estrone-3,4-quinone | Metabolite | pubchem.compound:114862 | |
| COMT | GeneProduct | ensembl:ENSG00000093010 | |
| UGT1A8 | GeneProduct | ensembl:ENSG00000167165 | |
| CYP1A2 | GeneProduct | ensembl:ENSG00000140505 | |
| UGT1A1 | GeneProduct | ncbigene:54658 | |
| SULT1E1 | GeneProduct | ensembl:ENSG00000109193 | |
| SULT1A1 | GeneProduct | ensembl:ENSG00000196502 | |
| ARSE | GeneProduct | ensembl:ENSG00000157399 | |
| NQO1 | GeneProduct | ensembl:ENSG00000181019 | |
| CYP3A4 | GeneProduct | ensembl:ENSG00000160868 | |
| CYP1A1 | GeneProduct | ensembl:ENSG00000140465 | |
| UGT2B7 | GeneProduct | ensembl:ENSG00000171234 | |
| UGT1A9 | GeneProduct | ncbigene:54600 | |
| GSTA1 | GeneProduct | ensembl:ENSG00000243955 | |
| UGT1A3 | GeneProduct | ncbigene:54659 | |
| GSTM1 | GeneProduct | ensembl:ENSG00000134184 | |
| ARSC | GeneProduct | ncbigene:412 | |
| ARSD | GeneProduct | ensembl:ENSG00000006756 | |
| CYP1B1 | GeneProduct | ensembl:ENSG00000138061 |
References
- Molecular origin of cancer: catechol estrogen-3,4-quinones as endogenous tumor initiators. Cavalieri EL, Stack DE, Devanesan PD, Todorovic R, Dwivedy I, Higginbotham S, et al. Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10937–42. PubMed Europe PMC Scholia
- Estrogen metabolism by conjugation. Raftogianis R, Creveling C, Weinshilboum R, Weisz J. J Natl Cancer Inst Monogr. 2000;(27):113–24. PubMed Europe PMC Scholia
- 2-Methoxyestradiol, a promising anticancer agent. Lakhani NJ, Sarkar MA, Venitz J, Figg WD. Pharmacotherapy. 2003 Feb;23(2):165–72. PubMed Europe PMC Scholia
- Functional implications of antiestrogen induction of quinone reductase: inhibition of estrogen-induced deoxyribonucleic acid damage. Bianco NR, Perry G, Smith MA, Templeton DJ, Montano MM. Mol Endocrinol. 2003 Jul;17(7):1344–55. PubMed Europe PMC Scholia
- Relative imbalances in estrogen metabolism and conjugation in breast tissue of women with carcinoma: potential biomarkers of susceptibility to cancer. Rogan EG, Badawi AF, Devanesan PD, Meza JL, Edney JA, West WW, et al. Carcinogenesis. 2003 Apr;24(4):697–702. PubMed Europe PMC Scholia
- Metabolic inactivation of estrogens in breast tissue by UDP-glucuronosyltransferase enzymes: an overview. Guillemette C, Bélanger A, Lépine J. Breast Cancer Res. 2004;6(6):246–54. PubMed Europe PMC Scholia
- Estradiol metabolites as isoform-specific inhibitors of human glutathione S-transferases. Abel EL, Lyon RP, Bammler TK, Verlinde CLMJ, Lau SS, Monks TJ, et al. Chem Biol Interact. 2004 Dec 30;151(1):21–32. PubMed Europe PMC Scholia
- Genetic polymorphisms in human SULT1A1 and UGT1A1 genes associate with breast tumor characteristics: a case-series study. Shatalova EG, Walther SE, Favorova OO, Rebbeck TR, Blanchard RL. Breast Cancer Res. 2005;7(6):R909-21. PubMed Europe PMC Scholia