Cell-Based Assays for Screening Androgen Receptor Ligands

The androgen receptor (AR, NR3C4) mediates the majority of androgen effects on target cells. The AR is activated following ligand binding that result is enhanced of target gene transcription. Several cell-based model systems have been developed that allow sensitive detection and monitoring of steroids or other compounds with AR bioactivity. Most cell-based AR reporter models use transgenic gene constructs that include an androgen response element that controls reporter gene expression. The DNA cis-regulatory elements that respond to AR share sequence similarity with cis-regulatory elements for glucocorticoid (GR, NR3C1), mineralocorticoid (MR, NR3C2), and progesterone (PGR, NR3C3) receptors, which has compromised AR selectivity for some models. In recent years, the sensitivity and selectivity of AR bioassays have been significantly improved through careful selection of cell models, utilization of improved reporter genes, and the use of yeast two-hybrid AR systems. This review summarizes and compares the currently available androgen-responsive cell model systems.