Convergence of two repressors through heterodimer formation of androgen receptor and testicular orphan receptor-4: A unique signaling pathway in the steroid receptor superfamily

The androgen receptor (AR) binds to androgen response elements and regulate s target genes via a mechanism involving coregulators. Here we demonstrate that the AR can interact with the testicular orphan receptor-4 (TR4) and fu nction as a repressor to down-regulate the TR4 target genes by preventing t he TR4 binding to its target DNA. Interestingly, the heterodimerization of AR and TR4 also allows TR4 to repress AR target gene expression. Simultaneo us exposure to both receptors therefore could result in bidirectional suppr ession of their target genes. Together, these data demonstrate that the cou pling of two different receptors, through the heterodimerization of AR and TR4, is a unique signaling pathway in the steroid receptor superfamily, whi ch may facilitate further understanding of the complicated androgen action in prostate cancer or libido.