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 Weitz

Activity

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Cited In

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Organisms

Homo sapiens

Communities

Annotations

Pathway Ontology

C18-steroid hormone biosynthetic pathway steroid hormone biosynthetic pathway

Participants

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

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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