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5α-Reductase Isozymes in Castration-Recurrent Prostate Cancer

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Androgen Action in Prostate Cancer

Abstract

Intracrine biosynthesis of dihydrotestosterone is the final step in anabolic androgen metabolism in the prostate. The NADPH-dependent steroid 5α-reductase isozymes irreversibly catalyze 5α-reduction of intracellular testosterone to dihydrotestosterone. In castration-recurrent prostate cancer mean mRNA levels suggest relative gene expression gradients of 5α-reductase-3 > 5α-reductase-1 ≫ 5α-reductase-2. Furthermore, sufficient levels of testosterone and dihydrotestosterone were observed in castration-recurrent prostate cancer to activate androgen receptor signaling pathway. In intact and recurrent CWR22 human xenografts, persistent dihydrotestosterone formation was observed after pretreatment with dutasteride. Improved inhibitors that target 5α-reductase-1, 2 and 3 isozymes may stop intraprostatic DHT biosynthesis and prevent the development of clinical prostate cancer or its progression.

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  1. Department of Urologic Oncology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA

    Mark A. Titus

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James Mohler Donald Tindall

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Titus, M.A., Mohler, J.L. (2009). 5α-Reductase Isozymes in Castration-Recurrent Prostate Cancer. In: Mohler, J., Tindall, D. (eds) Androgen Action in Prostate Cancer. Springer, New York, NY. https://doi.org/10.1007/978-0-387-69179-4_8

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