Intratissular androgens in benign prostatic hyperplasia and prostatic cancer

Abstract

The well-known hormone dependency of the normal human prostate and of BPH and prostatic carcinoma stimulated the study of cellular events which would possibly lead to specific steroid hormone patterns under the respective prevailing condition. In extending earlier observations on a significant DHT and E2 accumulation especially in stromal nuclei of BPH recent data on the uptake and metabolism of adrenal androgens clearly underline the important differential role of either stromal or epithelial cells. Epithelium and stroma of BPH contained a quantitatively different pattern of steroid metabolizing enzymes. This dualism of enzyme activity favours the conversion of testosterone to DHT in the stroma while androgens of adrenal origin are metabolized mainly in BPH epithelium. Further to quantitative data on the intracellular distribution of the three sex steroid classes (estrogens, androgens, adrenal androgens) and to Km and Vmax values of the respective steroid metabolizing enzymes in question (5 alpha-reductase, 3 alpha/beta-HSDH, 17 beta-HSDH, sulfatase, aromatase) the impact of antihormones (cyproterone acetate) on the intratissular distribution and on the in vivo cytosolic and nuclear binding of DHT as well as on its biological implications will be discussed. The data present a complicated picture, which points to special roles of epithelial and stromal cells and allow speculations on the relative importance of testicular and adrenal androgens and estrogens for the development and maintenance of both normal and diseased human prostates. Furthermore, the determination of intratissular steroid concentrations can be an important tool to understand and to ground a rational basis for a hormonal treatment of prostatic tumors.