AIM To screen new anti-prostatic hyperplasia drugs LTZ-8 and others(testosterone derivatives with different groups at C-3, C-4 and C-17), which are different structures of steroid 5α-reductase inhibitors. METHODS Isotope screening method was used to determine the ability of LTZ-8 to inhibit steroid 5α-reductase in vitro. Healthy male rats, which were castrated and injected testosterone to induce the regrowth of glandular cells, were selected as animal model. LTZ-8 was given orally once a day (3, 10 and 30 mg*kg-1) for 30 d. Wet and dry prostate weight was quantified and morphological structures of prostate were detected under light microscope. RESULTS LTZ-1, LTZ-5, LTZ-6 and LTZ-8 showed inhibitory effect on the activity of 5α-reductase,and LTZ-8 was the most effective one [Ki=(21.0±2.2)nmol*L-1]. Both the wet and dry prostate weight was reduced by 82% and 86% in LTZ-8 treated group (30 mg*kg-1) compared with control group respectively (P<0.05). Prostatic glandular cell height and acinar luminal area were decreased by LTZ-8 treatment in a dose-dependent manner. CONCLUSIONLTZ-8 inhibits steroid 5α-reductase activity in vitro and blocks the prostatic hyperplasia in testosterone-induced castrated rats.%目的为筛选新的不同结构的甾体5α-还原酶抑制剂LTZ-8等抗前列腺增生药物(在C-3, C-4, C-17具有不同基团的睾酮衍生物).方法同位素筛选法检测LTZ-8对体外5α-还原酶的抑制能力.体内动物模型选用去势大鼠(注射丙酸睾酮刺激前列腺重新生长),连续灌胃LTZ-8(3, 10 及 30 mg*kg-1,每日1次)30 d,检测前列腺组织绝对重量和相对重量,并对前列腺上皮进行组织形态学分析.结果 LTZ-1, LTZ-5, LTZ-6和LTZ-8均有抑制5α-还原酶的作用,其中LTZ-8的作用最强[Ki＝(21.0±2.2)nmol*L-1].大鼠口服30 mg*kg-1 LTZ-8,前列腺湿重和干重分别为对照组的82%和86%(P<0.05).前列腺上皮细胞高度和腺腔面积呈剂量依赖性下降.结论 LTZ-8具有抑制5α-还原酶的活性,并能抑制去势大鼠注射丙酸睾酮引起的前列腺增生.
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