Dadras S S, Cai X, Abasolo I, Wang Z
Department of Urology, Northwestern University Medical School, Chicago, IL 60611, USA.
Gene Expr. 2001;9(4-5):183-94. doi: 10.3727/000000001783992551.
The growth and development of some of the male sex accessory organs such as the prostate requires the conversion of testosterone to dihydrotestosterone (DHT) by 5alpha-reductase. To provide insights into the role of testosterone versus DHT in the prostate, we studied the impact of finasteride, a potent and specific inhibitor of 5alpha-reductase, on the expression of prostatic androgen-response genes in testis-intact rats and in 7-day castrated rats. Finasteride inhibition of the conversion of testosterone to DHT was confirmed by measuring serum and intraprostatic androgens. As expected, finasteride treatment caused a reduction in the wet weight of the prostate in the testis-intact rats and inhibited the testosterone-stimulated prostatic regrowth in the 7-day castrated rats. Although finasteride treatment had little or no effect on the expression of the surveyed androgen-response genes in testis-intact rats, its administration enhanced the expression of many androgen-response genes during the testosterone-stimulated regrowth of the regressed prostate in castrated rats. These observations suggest that testosterone is more potent than DHT in stimulating the expression of many androgen-response genes in the regressed prostate. The expression of androgen-response genes is mainly prostate specific and thus is likely to be associated with androgen-dependent prostatic differentiation. Therefore, testosterone is more potent than DHT in inducing differentiation and weaker in stimulating proliferation during prostate regrowth. The fact that testosterone is a strong inducer of prostatic differentiation has potential clinical implications.
一些男性附属器官（如前列腺）的生长和发育需要5α-还原酶将睾酮转化为双氢睾酮（DHT）。为了深入了解睾酮与DHT在前列腺中的作用，我们研究了5α-还原酶的强效特异性抑制剂非那雄胺对睾丸完整大鼠和去势7天大鼠前列腺雄激素反应基因表达的影响。通过测量血清和前列腺内雄激素证实了非那雄胺对睾酮向DHT转化的抑制作用。正如预期的那样，非那雄胺治疗导致睾丸完整大鼠的前列腺湿重减轻，并抑制了去势7天大鼠中睾酮刺激的前列腺再生。虽然非那雄胺治疗对睾丸完整大鼠中所检测的雄激素反应基因的表达几乎没有影响，但其给药增强了去势大鼠中睾酮刺激的退化前列腺再生过程中许多雄激素反应基因的表达。这些观察结果表明，在刺激退化前列腺中许多雄激素反应基因的表达方面，睾酮比DHT更有效。雄激素反应基因的表达主要是前列腺特异性的，因此可能与雄激素依赖性前列腺分化有关。因此，在前列腺再生过程中，睾酮在诱导分化方面比DHT更有效，而在刺激增殖方面则较弱。睾酮是前列腺分化的强诱导剂这一事实具有潜在的临床意义。
