Rittmaster R S, Norman R W, Thomas L N, Rowden G
Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
J Clin Endocrinol Metab. 1996 Feb;81(2):814-9. doi: 10.1210/jcem.81.2.8636309.
Finasteride, a 5 alpha-reductase inhibitor, decreases prostate size and improves symptoms in men with benign prostatic hyperplasia. However, little is known about prostate histopathology in men taking finasteride. To determine the mechanism by which finasteride reduces prostate size, tissue was collected at the time of prostatectomy from men taking either no medication (n = 10) or 5 mg finasteride daily for 6-18 days (n = 6; group 1), 23-73 days (n = 5; group 2), or 3 months to 4 yr (n = 5; group 3). To assess whether finasteride causes epithelial atrophy, morphometric measurement of epithelial cell and duct width was used. The mean epithelial cell width in control prostates (mean +/- SEM, 21 +/- 0.7 microns) decreased with duration of treatment to 19 +/- 1 microns in group 1, 15 +/- 2 microns in group 2, and 8 +/- 0.3 microns in group 3. Mean duct width decreased from 135 +/- 6 microns in the control prostates to 128 +/- 10 microns in group 1, 103 +/- 3 microns in group 2, and 63 +/- 6 microns in group 3. To assess whether prostate cell death was occurring, sections were in situ end labeled for DNA breaks and immunostained for tissue transglutaminase (tTG), a marker of apoptosis (programmed cell death). The percentage of epithelial cells staining for DNA breaks was 0.4 +/- 0.2 in control prostates, 2.8 +/- 0.9 in group 1, 1.7 +/- 0.5 in group 2, and 0.7 +/- 0.3 microns in group 3. Anti-tTG staining of epithelial cells was graded on a scale of 0-4. In control prostates, 3 +/- 1% of the ducts were grade 3 or 4 (> 50% of epithelial cells staining). In finasteride-treated prostates, 2 +/- 2% of the prostates in group 1, 13 +/- 4% of the prostates in group 2, and 0.5 +/- 0.5% of the prostates in group 3 were grade 3-4. These results indicate that a progressive decrease in epithelial cell size and function occurs during the first several months in the prostates of men treated with finasteride. The staining for DNA breaks and the tTG staining also indicate that an increased rate of apoptosis is occurring transiently in these prostates. We conclude that finasteride causes prostate involution through a combination of atrophy and cell death.
非那雄胺是一种5α还原酶抑制剂，可减小前列腺体积并改善良性前列腺增生男性的症状。然而，对于服用非那雄胺的男性的前列腺组织病理学情况却知之甚少。为了确定非那雄胺减小前列腺体积的机制，在前列腺切除术时收集了未服用任何药物的男性（n = 10）以及每天服用5毫克非那雄胺6 - 18天（n = 6；第1组）、23 - 73天（n = 5；第2组）或3个月至4年（n = 5；第3组）的男性的组织。为了评估非那雄胺是否会导致上皮萎缩，采用了上皮细胞和导管宽度的形态计量学测量方法。对照前列腺中的平均上皮细胞宽度（平均值±标准误，21±0.7微米）随着治疗时间的延长而减小，在第1组中降至19±1微米，在第2组中降至15±2微米，在第3组中降至8±0.3微米。平均导管宽度从对照前列腺中的135±6微米降至第1组中的128±10微米,第2组中的103±3微米，以及第3组中的63±6微米。为了评估前列腺细胞死亡是否正在发生，对切片进行原位末端标记以检测DNA断裂，并进行免疫染色以检测组织转谷氨酰胺酶（tTG），这是一种凋亡（程序性细胞死亡）的标志物。对照前列腺中DNA断裂染色阳性的上皮细胞百分比为0.4±0.2，第1组为2.8±0.9，第2组为1.7±0.5，第3组为0.7±0.3微米。上皮细胞的抗tTG染色按0 - 4级进行评分。在对照前列腺中，3±1%的导管为3级或4级（>50%的上皮细胞染色）。在非那雄胺治疗的前列腺中，第1组中2±2%的前列腺、第2组中13±4%的前列腺以及第3组中0.5±0.5%的前列腺为3 - 4级。这些结果表明，在接受非那雄胺治疗的男性前列腺中，上皮细胞大小和功能在前几个月会逐渐下降。DNA断裂染色和tTG染色也表明这些前列腺中凋亡率会短暂升高。我们得出结论，非那雄胺通过萎缩和细胞死亡的共同作用导致前列腺 involution（此处involution可能有误，推测是 involution，意为退化）。
