Estrogen metabolism (WP697)

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]
last edited

Authors

Pieter Giesbertz, AlexanderPico, MaintBot, Mkutmon, Zari, Egonw, DeSl, and Khanspers

Cited In

Organism

Homo sapiens

Communities

Annotations

Pathway Ontology: C18-steroid hormone biosynthetic pathway

Participants

Label Type Compact Identifier
2-Hydroxyestrone Metabolite hmdb:HMDB0000343
COMT GeneProduct ensembl:ENSG00000093010
UGT1A8 GeneProduct ensembl:ENSG00000167165
CYP1A2 GeneProduct ensembl:ENSG00000140505
Estrone Metabolite hmdb:HMDB0000145
UGT1A1 GeneProduct ncbigene:54658
UGT1A1 GeneProduct ncbigene:54658
4-hydroxyestradiol Metabolite pubchem.compound:5282360
SULT1E1 GeneProduct ensembl:ENSG00000109193
COMT GeneProduct ensembl:ENSG00000093010
UGT1A8 GeneProduct ensembl:ENSG00000167165
4-Methoxyestradiol-3-glucuronide Metabolite None
SULT1A1 GeneProduct ensembl:ENSG00000196502
2-Methoxyestradiol-3-glucuronide Metabolite hmdb:HMDB0006765
ARSE GeneProduct ensembl:ENSG00000157399
2-Hydroxyestradiol Metabolite hmdb:HMDB0000338
Estradiol sulfate Metabolite pubchem.compound:66416
Estrone sulfate Metabolite hmdb:HMDB0001425
2-hydroxyestradiol-3-glucuronide Metabolite None
UGT1A8 GeneProduct ensembl:ENSG00000167165
NQO1 GeneProduct ensembl:ENSG00000181019
Oxygen Metabolite hmdb:HMDB0001377
CYP3A4 GeneProduct ensembl:ENSG00000160868
Oxygen Metabolite hmdb:HMDB0001377
UGT1A1 GeneProduct ncbigene:54658
ESTRADIOL Metabolite chebi:23965
CYP1A1 GeneProduct ensembl:ENSG00000140465
SULT1A1 GeneProduct ensembl:ENSG00000196502
Oxygen Metabolite hmdb:HMDB0001377
Oxygen Metabolite hmdb:HMDB0001377
2-hydroxy-estradiol-2-glucuronide Metabolite None
UGT2B7 GeneProduct ensembl:ENSG00000171234
UGT1A8 GeneProduct ensembl:ENSG00000167165
4-hydroxyestrone Metabolite pubchem.compound:9971251
Estrone-2,3-quinone Metabolite pubchem.compound:148381
16a-Hydroxyestrone Metabolite hmdb:HMDB0000335
COMT GeneProduct ensembl:ENSG00000093010
2-Methoxyestrone 3-glucuronide Metabolite hmdb:HMDB0004482
Estradiol-3,4-semiquinone Metabolite None
2-Hydroxyestrone-3-glucuronide Metabolite None
4-hydroxyestrone-3-glucuronide Metabolite chebi:136969
Estrone-2,3-semiquinone Metabolite None
UGT1A9 GeneProduct ncbigene:54600
Estradiol-3-glucuronide Metabolite hmdb:HMDB0006224
Superoxide Metabolite hmdb:HMDB0002168
UGT1A8 GeneProduct ensembl:ENSG00000167165
UGT1A1 GeneProduct ncbigene:54658
UGT1A8 GeneProduct ensembl:ENSG00000167165
COMT GeneProduct ensembl:ENSG00000093010
UGT1A9 GeneProduct ncbigene:54600
UGT1A8 GeneProduct ensembl:ENSG00000167165
4-Methoxyestrone-3-glucuronide Metabolite chebi:137965
CYP1A2 GeneProduct ensembl:ENSG00000140505
Superoxide Metabolite hmdb:HMDB0002168
GSTA1 GeneProduct ensembl:ENSG00000243955
UGT2B7 GeneProduct ensembl:ENSG00000171234
CYP3A4 GeneProduct ensembl:ENSG00000160868
2-Methoxyestradiol Metabolite hmdb:HMDB0000405
UGT1A1 GeneProduct ncbigene:54658
2-hydroxy-estradiol-sulfate Metabolite None
Estradiol-3,4-quinone Metabolite hmdb:HMDB0060085
Superoxide Metabolite hmdb:HMDB0002168
Estradiol-2,3-semiquinone Metabolite None
Estradiol-17-glucuronide Metabolite pubchem.compound:5281887
UGT1A8 GeneProduct ensembl:ENSG00000167165
UGT1A8 GeneProduct ensembl:ENSG00000167165
UGT1A3 GeneProduct ncbigene:54659
Estrone-17-glucuronide Metabolite hmdb:HMDB0004483
GSTM1 GeneProduct ensembl:ENSG00000134184
ARSC GeneProduct ncbigene:412
Estrone-3,4-semiquinone Metabolite None
CYP1A1 GeneProduct ensembl:ENSG00000140465
4-hydroxy-estradiol-4-glucuronide Metabolite cas:90746-94-4
Estradiol-2,3-quinone Metabolite hmdb:HMDB0060084
4-hydroxy-estradiol-sulfate Metabolite None
4-Methoxyestradiol Metabolite hmdb:HMDB0000405
NQO1 GeneProduct ensembl:ENSG00000181019
Estrone-3-glucuronide Metabolite hmdb:HMDB0004483
ARSD GeneProduct ensembl:ENSG00000006756
UGT1A1 GeneProduct ncbigene:54658
UGT2B7 GeneProduct ensembl:ENSG00000171234
SULT1A1 GeneProduct ensembl:ENSG00000196502
Superoxide Metabolite hmdb:HMDB0002168
2-Methoxyestrone Metabolite hmdb:HMDB0000010
4-Methoxyestrone Metabolite pubchem.compound:194066
Estrone-3,4-quinone Metabolite pubchem.compound:114862
CYP1B1 GeneProduct ensembl:ENSG00000138061

References

  1. Cavalieri EL, Stack DE, Devanesan PD, Todorovic R, Dwivedy I, Higginbotham S, et al. Molecular origin of cancer: catechol estrogen-3,4-quinones as endogenous tumor initiators. Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10937–42. PubMed Europe PMC Scholia
  2. Raftogianis R, Creveling C, Weinshilboum R, Weisz J. Estrogen metabolism by conjugation. J Natl Cancer Inst Monogr. 2000;(27):113–24. PubMed Europe PMC Scholia
  3. Lakhani NJ, Sarkar MA, Venitz J, Figg WD. 2-Methoxyestradiol, a promising anticancer agent. Pharmacotherapy. 2003 Feb;23(2):165–72. PubMed Europe PMC Scholia
  4. Bianco NR, Perry G, Smith MA, Templeton DJ, Montano MM. Functional implications of antiestrogen induction of quinone reductase: inhibition of estrogen-induced deoxyribonucleic acid damage. Mol Endocrinol. 2003 Jul;17(7):1344–55. PubMed Europe PMC Scholia
  5. Rogan EG, Badawi AF, Devanesan PD, Meza JL, Edney JA, West WW, et al. Relative imbalances in estrogen metabolism and conjugation in breast tissue of women with carcinoma: potential biomarkers of susceptibility to cancer. Carcinogenesis. 2003 Apr;24(4):697–702. PubMed Europe PMC Scholia
  6. Guillemette C, Bélanger A, Lépine J. Metabolic inactivation of estrogens in breast tissue by UDP-glucuronosyltransferase enzymes: an overview. Breast Cancer Res. 2004;6(6):246–54. PubMed Europe PMC Scholia
  7. Abel EL, Lyon RP, Bammler TK, Verlinde CLMJ, Lau SS, Monks TJ, et al. Estradiol metabolites as isoform-specific inhibitors of human glutathione S-transferases. Chem Biol Interact. 2004 Dec 30;151(1):21–32. PubMed Europe PMC Scholia
  8. Shatalova EG, Walther SE, Favorova OO, Rebbeck TR, Blanchard RL. Genetic polymorphisms in human SULT1A1 and UGT1A1 genes associate with breast tumor characteristics: a case-series study. Breast Cancer Res. 2005;7(6):R909-21. PubMed Europe PMC Scholia