Suppression of estrogenic activity of 17β-estradiol by β-cyclodextrin

The suppressive effects of cyclodextrins (CDs) on the strong estrogenic activity of 17β-estradiol (E2) in water environments were investigated in this study. Cyclodextrins are doughnut-shaped molecules that possess a hydrophobic cavity and a hydrophilic exterior. The cavity can incorporate nonpolar molecules as guests to form inclusion complexes. β-CD and 2-hydroxypropyl-β-CD (HP-β-CD) were the most successful in forming a complex with E2 and improving its low aqueous solubility. The E2/CDs complexes bound to the estrogen receptor in a cell-free system as determined by ELISA and suppressed the hormone activities as measured by a yeast two-hybrid assay. These results indicate that hydrophobic E2 is easily transported through the lipid zone of the plasma membrane into the target cell and can bind to the nuclear receptor. However, the hydrophilic E2/β-CD and E2/HP-β-CD complexes do not penetrate the membrane. Therefore, these CDs are able to suppress the hormone activity of E2 through complex formation.