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Reduced Levels of 5-α Reductase 2 in Adult Prostate Tissue and Implications for BPH Therapy
Yinong Niu, M.D., PhD., Christian Diaz, M.D., Rongbin Ge, M.D., PhD., Zongwei Wang, M.D., PhD., Chin-Lee Wu, M.D., PhD., Aria F. Olumi, M.D..
Massachusetts General Hospital, Boston, MA, USA.

BACKGROUND: 5-alpha reductase 2 (5-AR 2) is responsible for conversion of testosterone to DHT, and it plays a critical role in proper development of external genitalia. Inhibition of 5-AR 2 by Finasteride for treatment of lower urinary tract symptoms for benign prostatic hyperplasia (BPH) is very common. Here we wished to determine why some adult human prostate tissues do not express 5-alpha reductase 2 (5-AR2), and hypothesized that methylation of 5-AR promoter region is correlate with low expression of 5-AR 2.
METHODS: The transition zone of 42 human prostate tissues after radical prostatectomy was used for evaluation. The initial 21 paraffin embedded samples were used for assessment of immunoreactivity to 5-AR 2 antibody in non-cancerous BPH samples. In the next 21 samples, fresh frozen prostate transition zone samples without cancer were assessed for immunoreactivity and RNA expression of 5-AR2. Methylation of 5-AR2 promoter was assessed in BPH-1 cell lines and benign human prostate samples by using methyl-specific PCR. Chi-square modeling was used for correlation.
RESULTS: We found that 6/21 (29%) of benign human prostate samples did not express the 5-AR 2 protein. We found that the promoter region of 5-AR 2 contains a CpG island that is methylated in benign prostate epithelial cells in culture and also in 39% (7/18) human prostate tissues. We found a strong correlation between methylation of the 5-AR 2 promoter region and absence of 5-AR 2 protein expression (p=0.0025, Fisher’s exact test).
CONCLUSIONS: Methylation of 5-AR 2 promoter region may account for low or absent expression of 5-AR 2 in human adult prostate tissues. Low or absent levels of 5-AR 2 in human prostate tissue may have implications in long term prostatic growth rate and treatment strategies for management of BPH.


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