5α-reductase type 3 expression in human benign and malignant tissues: A comparative analysis during prostate cancer progression

BACKGROUND A third isozyme of human 5α‐steroid reductase, 5α‐reductase‐3, was identified in prostate tissue at the mRNA level. However, the levels of 5α‐reductase‐3 protein expression and its cellular localization in human tissues remain unknown. METHODS A specific monoclonal antibody was developed, validated, and used to characterize for the first time the expression of 5α‐reductase‐3 protein in 18 benign and 26 malignant human tissue types using immunostaining analyses. RESULTS AND CONCLUSIONS In benign tissues, 5α‐reductase‐3 immunostaining was high in conventional androgen‐regulated human tissues, such as skeletal muscle and prostate. However, high levels of expression also were observed in non‐conventional androgen‐regulated tissues, which suggest either multiples target tissues for androgens or different functions of 5α‐reductase‐3 among human tissues. In malignant tissues, 5α‐reductase‐3 immunostaining was ubiquitous but particularly over‐expressed in some cancers compared to their benign counterparts, which suggests a potential role for 5α‐reductase‐3 as a biomarker of malignancy. In benign prostate, 5α‐reductase‐3 immunostaining was localized to basal epithelial cells, with no immunostaining observed in secretory/luminal epithelial cells. In high‐grade prostatic intraepithelial neoplasia (HGPIN), 5α‐reductase‐3 immunostaining was localized in both basal epithelial cells and neoplastic epithelial cells characteristic of HGPIN. In androgen‐stimulated and castration‐recurrent prostate cancer (CaP), 5α‐reductase‐3 immunostaining was present in most epithelial cells and at similar levels, and at levels higher than observed in benign prostate. Analyses of expression and functionality of 5α‐reductase‐3 in human tissues may prove useful for development of treatment for benign prostatic enlargement and prevention and treatment of CaP. Prostate 71:1033–1046, 2011. © 2010 Wiley‐Liss, Inc.