Androgen regulation of 5α-Reductase isoenzymes in prostate cancer: Implications for prostate cancer prevention

Jin Li, Zhiyong Ding, Zhengxin Wang, Jing Fang Lu, Sankar N. Maity, Nora M. Navone, Christopher J. Logothetis, Gordon B. Mills, Jeri Kim

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    37 Scopus citations

    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.

    Original languageEnglish (US)
    Article numbere28840
    JournalPloS one
    Volume6
    Issue number12
    DOIs
    StatePublished - Dec 14 2011

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)
    • Agricultural and Biological Sciences(all)

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    Li, J., Ding, Z., Wang, Z., Lu, J. F., Maity, S. N., Navone, N. M., Logothetis, C. J., Mills, G. B., & Kim, J. (2011). Androgen regulation of 5α-Reductase isoenzymes in prostate cancer: Implications for prostate cancer prevention. PloS one, 6(12), [e28840]. https://doi.org/10.1371/journal.pone.0028840