Studies on Regulation of Dihydrotestosterone Binding to and Releasing from the Androgen Receptor

The androgen receptor (AR) is a nuclear receptor that responds to testosterone and 5α-dihydrotestosterone (DHT) by modulating gene expression in a variety of cells, including prostate and muscle tissues. Studies of small molecule interaction with AR have shown diphenyl compounds inhibiting through a binding site labeled Binding Function 3 (BF3). The goal of this research is to analyze the interaction of the BF3 site with DDT and related compounds. Amino acids that are exposed on the surface of the BF3 that might interact with different compounds were mutated. Mutant proteins were tested experimentally for their impact on the inhibition the AR. Results show that mutations in F673, G724, and L830 prevent the inhibition of DDE, suggesting that DDE and related compounds act by interacting at the BF3 site of the AR. Understanding how the BF3 site binds with these compounds may lead to the development of new anticancer medications