Androgen Regulation of 5[alpha]-Reductase Isoenzymes in Prostate Cancer: Implications for Prostate Cancer Prevention

The enzyme 5[alpha]-reductase, which converts testosterone to dihydrotestosterone (DHT), performs key functions in the androgen receptor (AR) signaling pathway. The three isoenzymes of 5[alpha]-reductase identified to date are encoded by different genes: SRD5A1, SRD5A2, and SRD5A3. In this study, we...

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Bibliographic Details
Published inPloS one Vol. 6; no. 12; p. e28840
Main Authors Li, Jin, Ding, Zhiyong, Wang, Zhengxin, Lu, Jing-Fang, Maity, Sankar N, Navone, Nora M, Logothetis, Christopher J, Mills, Gordon B, Kim, Jeri
Format Journal Article
LanguageEnglish
Published Public Library of Science 14.12.2011
Subjects
Cancer prevention
Isoenzymes
Prevention
Prostate cancer
RNA
Testosterone
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Summary:The enzyme 5[alpha]-reductase, which converts testosterone to dihydrotestosterone (DHT), performs key functions in the androgen receptor (AR) signaling pathway. The three isoenzymes of 5[alpha]-reductase identified to date are encoded by different genes: SRD5A1, SRD5A2, and SRD5A3. In this study, we investigated mechanisms underlying androgen regulation of 5[alpha]-reductase isoenzyme expression in human prostate cells. We found that androgen regulates the mRNA level of 5[alpha]-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 5[alpha]-reductase isoenzymes may confer response or resistance to 5[alpha]-reductase inhibitors and thus may have importance in prostate cancer prevention.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0028840