From estrogen to androgen receptor: A new pathway for sex hormones in prostate

While all three coactivators ARA(70), steroid receptor coactivator 1, and RAC3/ACTR can enhance androgen receptor (AR) transcriptional activity at 1 nM dihydrotestosterone, we here demonstrate that only ARA(70) can induce AR transcriptional activity >30-fold in the presence of 10 nM 17β-estradiol (E2), but not diethylstilbestrol. The significance of this newly described E2-induced AR transcriptional activity in DU145 human prostate cancer cells was further strengthened by finding patients with Reifenstein partial-androgen-insensitive syndrome that fail in the E2-AR-ARA(70) pathway. Together, our data suggest, for the first time, testosterone/dihydrotestosterone may not be the only ligands for the AR. E2 represents another important natural ligand for AR that may play an essential role for the AR function and the development of the male reproductive system.