Role of cytochrome P450 in estradiol metabolism in vitro

Acta Pharmacol Sin. 2001 Feb;22(2):148-54.


Aim: Catechol estrogens and 16alpha-hydroxy estrogen are important metabolites that cause carcinogenesis. This study was aimed to stud y the role of cytochrome P450 in estradiol metabolism.

Methods: The estradiol metabolites were determined with HPLC-ECD. Correlation of estradiol metabolites production between cytochrome P450 activity, the inhibitory effect of specific inhibitors and enzyme catalyzing kinetics were studied in cDNA-expressed P450 or human liver microsomes.

Result: CYP1A2, CYP3A4, and CYP2C9 catalyze the estradiol 2-hydroxylation. CYP2C9, CYP2C19, and CYP2C8 have high activity in catalyzing 17beta-hydroxy dehydrogenation in cDNA expressed P450, but CYP1A2 is the most important enzyme in catalyzing estradiol 2-hydroxylation. Using furafyllin and troleandomycin to inhibit CYP1A2 and CYP3A4 in liver microsomes, it was found that the 2-hydroxylation had been inhibited about the same amount. This result suggests that in human liver microsomes CYP1A2 and CYP3A4 play an important role in 2-hydroxy estradiol formation. At low substrate concentration, 17beta -hydroxy dehydrogenation dominated the estradiol metabolism, but at high substrate concentration, 2-hydroxylation exceeded 17beta-hydroxy dehydrogenation to become the important mechanism.

Conclusion: CYP1A2 and CYP3A4 are two important enzymes catalyzing the main estradiol 2-hydroxylation metabolism pathway at high substrate concentrations. 17beta-hydroxy dehydrogenation is the main metabolism pathway at low concentrations, and CYP2C9, CYP2C19, and CYP2C8 may have high catalyzing activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cytochrome P-450 CYP1A2 / physiology*
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / physiology*
  • Estradiol / analogs & derivatives*
  • Estradiol / biosynthesis
  • Estradiol / metabolism*
  • Humans
  • In Vitro Techniques
  • Male
  • Microsomes, Liver / metabolism*


  • Estradiol
  • Cytochrome P-450 Enzyme System
  • 2-hydroxyestradiol
  • CYP3A protein, human
  • Cytochrome P-450 CYP1A2
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human