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.
Written by:
Li J, Ding Z, Wang Z, Lu JF, Maity SN, Navone NM, Logothetis CJ, Mills GB, Kim J. Are you the author?
Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Reference: PLoS One. 2011;6(12):e28840. Epub 2011 Dec 14.
PubMed Abstract
PMID: 22194926
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