Regulation of the transcriptional activity of the tyrosine hydroxylase gene by androgen receptor

Dopamine and the sex hormone testosterone are important factors regulating male sexual behavior. To investigate the possibility that these two factors are functionally interrelated, we investigated the potential role of the androgen receptor (AR) on transcriptional activity of the tyrosine hydroxylase (TH) gene that encodes the rate-limiting enzyme of the dopamine biosynthesis pathway. In this study, using transient co-transfection assays in TH-positive SK-N-BE(2)C and MN9D cells, we show that AR prominently transactivates TH promoter function in a ligand-dependent manner. Deletional and site-directed mutational analyses have mapped a putative androgen response element (ARE) in a region from −1562 to −1328 base pairs in the upstream TH promoter. We also found that DJ-1, one of recently identified genes whose mutations cause Parkinson's disease, down-regulated AR-dependent TH activation by approximately 50% in SK-N-BE(2)C cells. Based on these data, we propose that AR activates TH gene expression and that DJ-1 may modulate AR activity as a transcriptional co-repressor.