5α-reductase type 1 immunostaining is enhanced in some prostate cancers compared with benign prostatic hyperplasia epithelium

L. N. Thomas, R. C. Douglas, J. P. Vessey, R. Gupta, D. Fontaine, R. W. Norman, I. M. Thompson, D. A. Troyer, R. S. Rittmaster, C. B. Lazier

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Abstract

Purpose: In the prostate testosterone is converted to the more potent androgen dihydrotestosterone by the enzymes 5α-reductase (5αR) types 1 (5αR1) and 2 (5αR2). Since 5αR2 is the dominant prostatic enzyme, the 5αR2 selective inhibitor finasteride has been widely used to treat benign prostatic hyperplasia (BPH). However, inhibition of both 5αR enzymes provides a greater decrease in serum dihydrotestosterone. We developed a specific antibody to 5αR1 and assessed expression in BPH and prostate cancer (pCa) tissue. The presence of this isoenzyme in localized prostate cancer would provide a rationale for assessing the efficacy of dual inhibition for prostate cancer prevention. Materials and Methods: A polyclonal antibody to 5αR1 was developed and validated using 5αR1 and 5αR2 transfected COS-1 cells. A total of 26 BPH and 53 pCa specimens were assessed for 5αR1 protein expression using immunocytochemical methods. Also, 29 BPH and 37 pCa specimens were assayed for 5αR1 and 5αR2 enzyme activity. Results: Specificity of the 5αR1 antibody was confirmed using transfected COS-1 cells. Cells transfected with 5αR1 showed specific staining in immunocytochemistry experiments and on Western blotting of cell lysates the expected 24 kDa band was observed. High intensity immunoreactivity for 5αR1 was observed in the tumor epithelium of 28% of pCa specimens. No high intensity epithelial staining was observed in BPH specimens. In 19% of pCa and 7% of BPH specimens 5αR1 enzyme activity was detected. Conclusions: The presence of increased 5αR1 in some prostatic malignancies suggests that it is worthwhile to investigate the use of a dual 5αR inhibitor to prevent or treat early stage prostate cancer.

Original languageEnglish (US)
Pages (from-to)2019-2025
Number of pages7
JournalJournal of Urology
Volume170
Issue number5
DOIs
StatePublished - Nov 2003

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Keywords

  • Androgens
  • Prostate
  • Prostatic hyperplasia
  • Prostatic neoplasms

ASJC Scopus subject areas

  • Urology

Cite this

Thomas, L. N., Douglas, R. C., Vessey, J. P., Gupta, R., Fontaine, D., Norman, R. W., Thompson, I. M., Troyer, D. A., Rittmaster, R. S., & Lazier, C. B. (2003). 5α-reductase type 1 immunostaining is enhanced in some prostate cancers compared with benign prostatic hyperplasia epithelium. Journal of Urology, 170(5), 2019-2025. https://doi.org/10.1097/01.ju.0000091804.20183.81