Kyprianou N, Isaacs J T
Oncology Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Prostate. 1987;11(1):41-50. doi: 10.1002/pros.2990110106.
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.
前列腺双氢睾酮（DHT）剂量与前列腺细胞数量反应曲线的形状可用于确定雄激素诱导的前列腺细胞数量增加是随着前列腺DHT的所有水平持续分级增加的连续过程，还是该过程是量子性的，仅在达到前列腺DHT的临界阈值时才开始发生。为了做出这一判定，使用去势肾上腺切除大鼠、未接受治疗的去势大鼠以及接受不同长度填充睾酮的硅橡胶植入物的去势大鼠，构建了一条从检测不到到药理学高水平的前列腺DHT的前列腺DHT剂量/前列腺细胞数量反应曲线。发现该剂量反应曲线的形状并非连续双曲线，而是不连续的S形。这表明，在大鼠中，雄激素诱导的前列腺细胞数量增加是一个量子过程，只有当前列腺DHT浓度高于临界阈值时（即大鼠腹侧前列腺为0.4 ng/10⁸ 细胞）才会开始。因此，为了完全防止这种雄激素对前列腺细胞数量的刺激，必须将前列腺DHT水平降低到该临界阈值以下，但不必完全消除。
