Metabolism of Catecholestrogens and Agonistic Activity on Estrogen Receptor Dependent Gene Expression in MCF-7 Cells

Catecholestrogens (CE), namely 2-hydroxyestradiol (2-OH-E 2 ) and 4-hydroxyestradiol (4-OH-E 2 ), are important, naturally occurring metabolites of E 2 . We studied their role on estrogen dependent processes using the MCF-7 cell line as a model system. Incubations with 2-OH-E 2 and 4-OH-E 2 at 10 nM for 1 hour resulted in a tight nuclear binding of the estrogen receptor (ER). The pS2 mRNA in MCF-7 cells was increased by a two-day treatment with 10 nM 2-OH-E 2 or 4-OH-E 2 by 48% and 79%, respectively. Therefore, we conclude that the ER is transcriptionally active in MCF-7 cells upon binding of CE. Using radiolabeled CE we measured an intensive metabolism to the corresponding methyl ethers. Interestingly by paper chromatography we obtained strong evidence for the reversible formation of a complex containing CE under conventional cell culture conditions. Following formation of the complex, CE are still accessible to MCF-7 cells, bind the ER and induce ER dependent gene expression at the transcriptional level.