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. © 2009 Springer-Verlag New York.
CITATION STYLE
Titus, M. A., & Mohler, J. L. (2009). 5α-reductase isozymes in castration-recurrent prostate cancer. In Androgen Action in Prostate Cancer (pp. 175–185). Springer US. https://doi.org/10.1007/978-0-387-69179-4_8
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