Quantal relationship between prostatic dihydrotestosterone and prostatic cell content: critical threshold concept

Abstract

The shape of the prostatic dihydrotestosterone (DHT) dose vs prostatic cell number response curve can be used to determine if the androgen-induced increase in prostatic cell number occurs as a continuous graded process increasing with all levels of prostatic DHT, or whether the process is quantal, beginning to occur only when a critical threshold of prostatic DHT is reached. To make this determination, castrated-adrenalectomized rats, castrated rats given no treatment, and castrated rats given testosterone-filled silastic implants of varying lengths were used to construct such a prostatic DHT dose/prostatic cell number response curve ranging from undetectable to pharmacologically high levels of prostatic DHT. The shape of this dose-response curve was found not to be continuously hyperbolic, but instead, to be discontinuously sigmoidal. This demonstrates that, in the rat, androgen-induced increase in prostatic cell number occurs as a quantal process which can only begin when the concentration of prostatic DHT is above a critical threshold value (ie, 0.4 ng/10(8) cells for the rat ventral prostate). Thus, in order to completely prevent this androgenic stimulation of prostatic cell number, the prostatic DHT level has to be lowered to below this critical threshold but does not have to be completely eliminated.