Yeh S, Miyamoto H, Shima H, Chang C
George Whipple Laboratory for Cancer Research, Departments of Pathology, Urology, and Biochemistry, University of Rochester, Rochester, NY 14642, USA.
Proc Natl Acad Sci U S A. 1998 May 12;95(10):5527-32. doi: 10.1073/pnas.95.10.5527.
While all three coactivators ARA70, steroid receptor coactivator 1, and RAC3/ACTR can enhance androgen receptor (AR) transcriptional activity at 1 nM dihydrotestosterone, we here demonstrate that only ARA70 can induce AR transcriptional activity >30-fold in the presence of 10 nM 17beta-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-ARA70 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.
虽然三种共激活因子ARA70、类固醇受体共激活因子1和RAC3/ACTR在1 nM双氢睾酮存在时均能增强雄激素受体(AR)的转录活性,但我们在此证明,只有ARA70能在10 nM 17β-雌二醇(E2)而非己烯雌酚存在时诱导AR转录活性增加30倍以上。在患有赖芬斯坦部分雄激素不敏感综合征且E2-AR-ARA70通路存在缺陷的患者中发现这一现象,进一步证实了在DU145人前列腺癌细胞中这种新描述的E2诱导的AR转录活性的重要性。总之,我们的数据首次表明,睾酮/双氢睾酮可能不是AR的唯一配体。E2代表AR的另一种重要天然配体,可能对AR功能及男性生殖系统发育起着至关重要的作用。