Factors Controlling the Expression of 5α-Reductase in Human Prostate: A Possible New Approach for the Treatment of Prostate Cancer

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Abstract
The functional activity of the 5α-reductase isoenzyme in the human prostate is gradually depleted as the gland undergoes transformation from the normal to the metastatic state. There are two isoforms of this enzyme expressed in the prostate and recent studies have demonstrated that the type II isoenzyme is the one most affected by the onset of neoplasia. To elucidate the mechanism(s) responsible for the down-regulation of the isoenzyme activity, we re-examined the nature of the interaction between stroma and epithelial cells in the human prostate. We noted that the control of the isoenzyme expression in the epithelial cells was regulated by a paracrine factor specific to the prostate fibroblast. In the absence of this factor the human prostate loses its capacity to express the 5α-reductase type II isoenzyme – a characteristic manifested simultaneously with the loss of differentiation in the tissues. This finding presents a totally new concept to the control of 5α-reductase in the human prostate and offers a possibility for an interesting and alternative approach to the management of prostate cancer.

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