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PLoS One. 2011;6(12):e28840. doi: 10.1371/journal.pone.0028840. Epub 2011 Dec 14.

Androgen regulation of 5α-reductase isoenzymes in prostate cancer: implications for prostate cancer prevention.

Author information

1
Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.

Abstract

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.

PMID:
22194926
PMCID:
PMC3237548
DOI:
10.1371/journal.pone.0028840
[Indexed for MEDLINE]
Free PMC Article

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