Factors controlling the expression of 5 alpha-reductase in human prostate:A possible new approach for the treatment of prostate cancer

The functional activity of the 5 alpha-reductase isoenzyme in the human pro state is gradually depleted as the gland undergoes transformation from the normal to the metastatic state. There are two isoforms of this enzyme expre ssed 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 activ ity, we re-examined the nature of the interaction between stroma and epithe lial cells in the human prostate. We noted that the control of the isoenzym e expression in the epithelial cells was regulated by a paracrine factor sp ecific to the prostate fibroblast. In the absence of this factor the human prostate loses its capacity to express the 5 alpha-reductase type II isoenz yme - a characteristic manifested simultaneously with the loss of different iation in the tissues. This finding presents a totally new concept to the c ontrol of 5 alpha-reductase in the human prostate and offers a possibility for an interesting and alternative approach to the management of prostate c ancer.