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 activ ity at 1 nM dihydrotestosterone, we here demonstrate that only ARA(70) can induce AR transcriptional activity >30-fold in the presence of 10 nM 17 beta-estradiol (E2), but not diethylstilbestrol. The significan ce of this newly described E2-induced AR transcriptional activity in D U145 human prostate cancer cells was further strengthened by finding p atients with Reifenstein partial-androgen insensitive syndrome that fa il in the E2-AR-ARA(70) pathway. Together, our data suggest, for the f irst time, testosterone/dihydrotestosterone may not be the only ligand s for the AR E2 represents another important natural ligand for AR tha t may play an essential role for the AR function and the development o f the male reproductive system.