Wright A S, Thomas L N, Douglas R C, Lazier C B, Rittmaster R S
Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada.
J Clin Invest. 1996 Dec 1;98(11):2558-63. doi: 10.1172/JCI119074.
Although dihydrotestosterone (DHT) is the principal androgen in the prostate, testosterone can also act as an androgen in this tissue. To determine the relative potencies of testosterone and DHT in preventing prostate regression, castrated rats were implanted for 4 d with varying doses of testosterone in the presence or absence of the 5alpha-reductase inhibitor finasteride. In the absence of finasteride, testosterone in the prostate is converted to DHT, creating an intraprostatic DHT dose response. In the presence of finasteride, this conversion is blocked, and an intraprostatic testosterone dose response is achieved. DHT was 2.4 times more potent than testosterone at maintaining normal prostate weight and duct lumen mass, a measure of epithelial cell function. The two androgens were equipotent at preventing DNA fragementation and expression of testosterone-repressed prostate message, two measures of apoptosis (cell death). The intraprostatic testosterone concentration that results from finasteride treatment in rats is sufficient to inhibit apoptosis but will not maintain normal epithelial cell activity. In conclusion, whereas DHT is more potent than testosterone at stimulating prostate epithelial cell function as measured by ductal mass, the two androgens are equipotent at preventing prostate cell death after castration. These results explain why finasteride causes prostate involution in the rat with minimal evidence of prostate cell death.
尽管双氢睾酮（DHT）是前列腺中的主要雄激素，但睾酮在该组织中也可作为雄激素发挥作用。为了确定睾酮和DHT在预防前列腺萎缩方面的相对效力，对去势大鼠在存在或不存在5α-还原酶抑制剂非那雄胺的情况下植入不同剂量的睾酮，持续4天。在不存在非那雄胺的情况下，前列腺中的睾酮会转化为DHT，从而产生前列腺内DHT剂量反应。在存在非那雄胺的情况下，这种转化被阻断，从而实现前列腺内睾酮剂量反应。在维持正常前列腺重量和导管管腔质量（一种上皮细胞功能的指标）方面，DHT的效力比睾酮高2.4倍。这两种雄激素在预防DNA片段化和睾酮抑制的前列腺信息表达（细胞凋亡的两种指标）方面效力相当。非那雄胺处理大鼠后产生的前列腺内睾酮浓度足以抑制细胞凋亡，但无法维持正常上皮细胞活性。总之，以导管质量衡量，DHT在刺激前列腺上皮细胞功能方面比睾酮更有效，但在去势后预防前列腺细胞死亡方面，这两种雄激素效力相当。这些结果解释了为什么非那雄胺会导致大鼠前列腺萎缩，且几乎没有前列腺细胞死亡的证据。
