5α-Reductase-III and its potential in prevention/treatment of prostate cancer


There are in fact three so-called “isozymes” (slightly different versions) of the human enzyme 5α-steroid reductase. The activity of 5α-reductase-II can be affected by the 5α-reductase inhibitor (5-ARI) finasteride (Proscar); the activity of 5α-reductase-I and -II can be affected by the 5-ARI dutasteride (Avodart), but we know relatively little about the expression and cellular localization of 5α-reductase-III in human tissues. And we have no real idea of its potential impact on the development of either benign prostatic hyperplasia (BPH) or prostate cancer.

Godoy et al. have reported the use of a specific monoclonal antibody to investigate the expression of 5α-reductase-III in a variety of human tissue types.

Here is a quick summary of their key findings:

  • Expression of 5α-reductase-III was high in
    • Conventional androgen-regulated human tissues (e.g., skeletal muscle and prostate tissue)
    • Non-conventional androgen-regulated tissues, which suggest either multiples target tissues for androgens or different functions of 5α-reductase-3 among human tissues.
  • Expression of 5α-reductase-III was
    • Common to all malignant (cancerous) tissues tested
    • Higher than normal (“over-espressed”) in somce cancerous tissues compared to their benign counterparts
    • Localized to basal epithelial cells in benign prostate tissue
    • Not observed in secretory/luminal epithelial cells in benign prostate tissue
    • Localized in basal epithelial cells and neoplastic epithelial cells characteristic of high-grade prostatic intraepithelial neoplasia (HG-PIN)
    • Evident in most androgen-stimulated and castration-recurrent prostate cancer epithelial cells and sometimes at levels higher than observed in benign prostate tissue

The signifciance of these data are not yet fully appreciated, but they do suggest that:

  • There is a possible role for 5α-reductase-III as a biomarker of prostate malignancy.
  • There is a possible role for inhibition of 5α-reductase-III in the prevention and management of prostate cancer.

There will need to be a good deal more work before either of these possibilities might be shown to be clinically important, but given what we know about the effects of 5α-reductase-I and -II in the growth and development of prostate cancer, this would appear to be research worth following up on.

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