di Salle E, Giudici D, Briatico G, Ornati G, Panzeri A
Laboratory of endocrinology, R&D, Farmitalia Carlo Erba, Nerviano (MI), Italy.
J Steroid Biochem Mol Biol. 1993 Nov;46(5):549-55. doi: 10.1016/0960-0760(93)90181-u.
Turosteride [FCE 26073; 1-(4-methyl-3-oxo-4-aza-5 alpha-androstane-17 beta-carbonyl)-1,3- diisopropylurea] is a novel inhibitor of 5 alpha-reductase, the enzyme responsible for the conversion of testosterone (T) to 5 alpha-dihydrotestosterone (DHT). The compound caused inhibition of rat and human prostatic enzymes, with IC50 values of 55 and 53 nM, respectively. In addition, turosteride did not show any relevant binding affinity to the rat prostate androgen receptor (IC50 84 microM; relative binding affinity 0.004% of DHT). The endocrine effects of turosteride were evaluated in adult male rats, treated orally at daily doses of 3, 10 and 30 mg/kg for 20 days. At these doses, the compound reduced the ventral prostate weight by 10, 33 and 42% and the intraprostatic total DHT content by 61, 74 and 78%, respectively, whereas no change in the intraprostatic content of T was observed. Turosteride caused a 40% reduction of serum DHT levels which, however, did not reach statistical significance, whereas serum T levels were similar to control animals. No effect on serum luteinizing hormone or prolactin was observed. These results indicate that the antiprostatic effect of turosteride in the adult rat is related to inhibition of the conversion of T to DHT. However, at variance with other 5 alpha-reductase inhibitors (e.g. finasteride), turosteride caused a decrease in prostatic DHT not associated with a secondary increase in T content. This peculiarity of turosteride may represent an improvement of the compound over other inhibitors.
图罗司特（Turosteride）[FCE 26073；1-(4-甲基-3-氧代-4-氮杂-5α-雄甾烷-17β-羰基)-1,3-二异丙基脲]是一种新型5α-还原酶抑制剂，该酶负责将睾酮（T）转化为5α-双氢睾酮（DHT）。该化合物对大鼠和人前列腺酶有抑制作用，IC50值分别为55和53 nM。此外，图罗司特对大鼠前列腺雄激素受体没有任何显著的结合亲和力（IC50为84 μM；相对结合亲和力为DHT的0.004%）。对成年雄性大鼠口服给予图罗司特，剂量分别为3、10和30 mg/kg，持续20天，以评估其内分泌效应。在这些剂量下，该化合物使前列腺腹侧重量分别降低了10%、33%和42%，前列腺内总DHT含量分别降低了61%、74%和78%，而前列腺内T含量未观察到变化。图罗司特使血清DHT水平降低了40%，但未达到统计学显著性，而血清T水平与对照动物相似。未观察到对血清黄体生成素或催乳素的影响。这些结果表明，图罗司特在成年大鼠中的抗前列腺作用与抑制T向DHT的转化有关。然而，与其他5α-还原酶抑制剂（如非那雄胺）不同的是，图罗司特导致前列腺DHT降低，且与T含量的继发性增加无关。图罗司特的这一特性可能表明该化合物比其他抑制剂有所改进。
