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

Research output: Contribution to journalArticlepeer-review

42 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
Externally publishedYes

ASJC Scopus subject areas

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

Fingerprint

Dive into the research topics of 'Androgen regulation of 5α-Reductase isoenzymes in prostate cancer: Implications for prostate cancer prevention'. Together they form a unique fingerprint.

Cite this