Figure 1.

Disposition of 17β-estradiol (E2) and metabolites. SULT1A1 and UGT1A1 inactivate E2, and thus represent an antimitogenic pathway; the products of E2 oxidation, 2-hydroxyestradiol (2-OHE2) and 4-hydroxyestradiol, (4-OHE2), are both possible mutagens; 2-OHE2 is methylated by catechol-O-methyltransferase (COMT) to the antiproliferative compound 2-methoxyestradiol (2-MeE2), thus this pathway is potentially both antimutagenic and anitmitogenic. 2-OHE2 is alternatively sulfated and glucuronidated; this pathway would be predicted to be antimutagenic because it inactivates 2-OHE2 and, at the same time, promitogenic because it competes with the antimitogenic methylation pathway. 4-OHE2 is also inactivated by SULT1A1 and UGT1A1. Thus, sulfation and glucuronidation, depending on the cellular context and the competing metabolic pathways in a specific cell, may represent protective (detoxifying) or detrimental pathways. CYPs, Cytochromes P450.