Correlated Biochemical and Stereological Studies on Testosterone Metabolism in the Stromal and Epithelial Compartment of Human Benign Prostatic Hyperplasia

Abstract
The growth and function of the human prostate is dependent upon a continous supply of androgens, mainly 5.alpha.-dihydrotestosterone, the 5.alpha.-reduced metabolite of testosterone. Within the human prostate dihydrotestosterone is thought to be the intracellular mediator of androgen action. Dihydrotestosterone is evenly distributed between the stromal and epithelial compartment of the prostate, but the anatomical localization of dihydrotestosterone formation within the normal and hyperplastic prostate is still not established. Under conditions approximating the in vivo state, dihydrotestosterone formation was measured in prostates obtained from 4 men with normal prostates and 36 men with benign prostatic hyperplasia. Histometric analysis of the cellular composition of the samples incubated was performed in order to correlate the morphological an the histochemical findings. Dihydrotestosterone is the major metabolite, and androstanediol and androstenedione were formed in smaller quantities. Under the given conditions metabolite formation from testosterone increased linearly for 60 min and the half maximum rate of dihydrotestosterone formation (Km) was observed at about 1.25 .times. 10-6 M testosterone, a value similar to that reported for rat prostatic nuclei and human prostatic tissue. Dihydrotestosterone formation was higher in hyperplastic prostates than in the normal prostate. (Student''s test: P < 0.05). The stroma in both the normal and hyperplastic tissue converts testosterone to dihydrotestosterone very actively. No significant relation was found between dihydrotestosterone formation and the percent distribution of the stromal and epithelial compartment in any sample studied. The rate of dihydrotestosterone formation apparently is increased in the hyperplastic prostate and the rate of dihydrotestosterone formation is approximately the same in the epithelial and stromal compartments of the prostate.