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.
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.
Authors: Elise A Olsen; Maria Hordinsky; David Whiting; Dow Stough; Stuart Hobbs; Melissa L Ellis; Timothy Wilson; Roger S Rittmaster Journal: J Am Acad Dermatol Date: 2006-12 Impact factor: 11.527
Authors: Gerald L Andriole; David G Bostwick; Otis W Brawley; Leonard G Gomella; Michael Marberger; Francesco Montorsi; Curtis A Pettaway; Teuvo L Tammela; Claudio Teloken; Donald J Tindall; Matthew C Somerville; Timothy H Wilson; Ivy L Fowler; Roger S Rittmaster Journal: N Engl J Med Date: 2010-04-01 Impact factor: 91.245
Authors: Swaroop S Singh; Bahjat Qaqish; Jacqueline L Johnson; O Harris Ford; Julie F Foley; Susan J Maygarden; James L Mohler Journal: Anal Quant Cytol Histol Date: 2004-08 Impact factor: 0.302
Authors: Mario A Eisenberger; Menachem Laufer; Nicholas J Vogelzang; Oliver Sartor; Donald Thornton; Blake Lee Neubauer; Victoria Sinibaldi; Gary Lieskovsky; Michael A Carducci; Mariana Zahurak; Derek Raghavan Journal: Urology Date: 2004-01 Impact factor: 2.649
Authors: Michael Stanbrough; Glenn J Bubley; Kenneth Ross; Todd R Golub; Mark A Rubin; Trevor M Penning; Phillip G Febbo; Steven P Balk Journal: Cancer Res Date: 2006-03-01 Impact factor: 12.701
Authors: Tyler M Bauman; Priyanka D Sehgal; Karen A Johnson; Thomas Pier; Reginald C Bruskewitz; William A Ricke; Wei Huang Journal: Prostate Date: 2014-04-30 Impact factor: 4.104
Authors: P Sgrò; C Minganti; M Lista; C Antinozzi; M Cappa; Y Pitsiladis; F Pigozzi; L Di Luigi Journal: J Endocrinol Invest Date: 2020-09-18 Impact factor: 4.256
Authors: Mark A Titus; Yun Li; Olga G Kozyreva; Varun Maher; Alejandro Godoy; Gary J Smith; James L Mohler Journal: Prostate Date: 2013-10-22 Impact factor: 4.104