Changes in the metabolism of dihydrotestosterone in the hyperplastic human prostate

It has been well established that hyperplastic human prostatic tissue is characterized by a 3- to 4-fold elevation in the content of dihydrotestosterone (DHT) compared to that in normal prostatic tissue. However, the exact mechanism responsible for DHT accumulation has not been established. One hypothesis for the abnormal elevation of DHT content in hyperplastic prostatic tissue is that changes occur in the tissue itself which shift the overall balance of androgen metabolism favoring the increased accumulation of DHT. To test this hypothesis, the metabolic activities that produce and remove DHT were determined in a series of normal as well hyperplastic human prostates. The results of these studies demonstrated that in each of the eight separate hyperplastic prostatic tissues assayed, there was a significant increase in 5 alpha-reductase activity producing DHT concomitant with significant decreases in the 3 alpha- and 3 beta-hydroxysteroid oxidoreductase reductase and 17 beta-hydroxysteroid oxidoreductase oxidase activities removing DHT. These specific alterations result in a major shift in the overall balance of androgen metabolism which favors an increase in the net formation of DHT in hyperplastic prostatic tissue. Such a shift in androgen metabolism is, therefore, at least one mechanism for the well documented increase in DHT content found in hyperplastic human prostatic tissue.