Reduced levels of 5‐α reductase 2 in adult prostate tissue and implications for BPH therapy

Abstract

5-α reductase 2 (5-AR 2) is a key enzyme that is responsible of proper development of prostate tissue. Inhibition of 5-AR 2 has proven to be efficacious for management of urinary symptoms secondary benign prostatic hyperplasia (BPH). However, some patients are resistant to the therapeutic effects of 5-AR 2 inhibitor. We wished to determine why some benign non-cancerous adult human prostates do not express 5-AR 2, and hypothesized that methylation of 5-AR 2 promoter region correlated with low expression of 5-AR 2 protein. The transition zone of 42 human prostate tissues after radical prostatectomy was used for evaluation. Initially, 21 paraffin embedded samples were used to assess 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 methylation of the 5-AR 2 promoter using methyl-specific PCR. We show that 6/21 (29%) of benign human prostate samples did not express the 5-AR 2 protein. Moreover, 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 show 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). Methylation of 5-AR 2 promoter may account for low or absent expression of 5-AR 2 in some human adult prostate tissues.