A Comprehensive Investigation Into the Molecular Mechanism Responsible for Selective Androgen Receptor Modulator Tissue-Selectivity

The study investigated the molecular mechanism behind the tissue-selectivity of selective androgen receptor modulators (SARMs) by analyzing the conformation of the androgen receptor (AR) using various techniques. Despite initial challenges with biotinylation, further analysis revealed ligand-specific cofactors, notably identifying nuclear receptor corepressor (NCoR) exclusively in SARM-treated samples. This was confirmed by observing a higher degree of AR-SARM/NCoR association compared to AR-DHT/NCoR. Additionally, differences in cytoplasmic-nuclear transport and nuclear foci formation between AR-SARM and AR-DHT were noted. The findings suggested that AR-SARM complexes have distinct structural and functional properties, providing insights into the SARM tissue-selective mechanism and potential research directions.