5α-Reductase Isozymes in Castration-Recurrent Prostate Cancer

  • Mark A. Titus
  • James L. Mohler


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.


Androgen Receptor Tandem Mass Spectrometry Assay Carboxy Terminal Peptide Activate Androgen Receptor Signaling Human Male Urine 
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© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of Urologic Oncology, Roswell Park Cancer InstituteBuffaloUSA

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