Androgen regulation of 5α-reductase isoenzymes in prostate cancer: implications for prostate cancer prevention.
Androgen regulation of 5α-reductase isoenzymes in prostate cancer: implications for prostate cancer prevention.
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DOI：
10.1371/journal.pone.0028840
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Kim J
中科院分区：
文献类型：
--
作者：
Li J;Ding Z;Wang Z;Lu JF;Maity SN;Navone NM;Logothetis CJ;Mills GB;Kim J
将睾酮转化为二氢睾酮（DHT）的酶5α-还原酶在雄激素受体（AR）信号通路中发挥关键作用。目前发现的3种5α-还原酶同工酶由不同的基因编码：SRD 5A 1、SRD 5A 2和SRD 5A 3。在这项研究中，我们研究了雄激素调节人前列腺细胞5α-还原酶同工酶表达的机制。我们发现雄激素以细胞类型特异性方式调节5α-还原酶同工酶的mRNA水平，这种调节发生在转录水平，并且AR是这种调节所必需的。此外，我们的研究结果表明，AR在体内被募集到SRD 5A 3启动子上的负雄激素反应元件（nARE），并在体外直接与nARE结合。5α-还原酶同工酶的不同表达水平可能赋予对5α-还原酶抑制剂的应答或抗性，因此可能在前列腺癌预防中具有重要意义。
The enzyme 5α-reductase, which converts testosterone to dihydrotestosterone (DHT), performs key functions in the androgen receptor (AR) signaling pathway. The three isoenzymes of 5α-reductase identified to date are encoded by different genes: SRD5A1, SRD5A2, and SRD5A3. In this study, we investigated mechanisms underlying androgen regulation of 5α-reductase isoenzyme expression in human prostate cells. We found that androgen regulates the mRNA level of 5α-reductase isoenzymes in a cell type–specific manner, that such regulation occurs at the transcriptional level, and that AR is necessary for this regulation. In addition, our results suggest that AR is recruited to a negative androgen response element (nARE) on the promoter of SRD5A3 in vivo and directly binds to the nARE in vitro. The different expression levels of 5α-reductase isoenzymes may confer response or resistance to 5α-reductase inhibitors and thus may have importance in prostate cancer prevention.
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