COMPARATIVE ASPECTS OF PROSTATIC GROWTH AND ANDROGEN METABOLISM WITH AGING IN THE DOG VERSUS THE RAT

In untreated rats and dogs, there is a species-specific time period when proliferative growth of the prostate normally occurs during which the gland grows to its maximum normal cellular content. In both species, the prostate has reached its maximum normal cellular content, which requires 1 yr for the rat and 2 yr for the dog, net proliferative prostatic growth ceases and is replaced by a steady-state maintenance of the gland. When 2-yr-old dogs with starting prostates already at their maximum normal cellular content are subsequently treated for 4 mo. with dihydrotestosterone (DHT), such treatment induces an additional 2-fold abnormal proliferative increase in prostatic cell number above that seen in normal glands from untreated dogs of any age. In direct contrast to the dog, when rats are treated with exogenous DHT for as long as 650 days, such treatment cannot induce any abnormal overgrowth of the gland above the maximum size normally obtained by 365 days of life in untreated control rats. Studies of prostatic androgen metabolism suggest that the differential susceptibility of the dog and rat prostate to DHT-induced abnormal hyperplasia is related to the differential ability of DHT treatment to increase the gland''s ability for net DHT formation. This suggestion is based upon the fact that only in the DHT-treated dog, and not the rat, can such DHT treatment induce changes in several of the prostatic activities of DHT metabolism resulting in a 2.5-fold increase in the gland''s overall ability for net DHT formation. Changes in prostatic DHT metabolism which result in an increased prostatic ability for net DHT formation may be essential in abnormal hyperplasia of the prostate.