Ito K, Fukabori Y, Shibata Y, Suzuki K, Mieda M, Gotanda K, Honma S, Yamanaka H
Department of Urology, Gunma University School of Medicine, Maebashi, Japan.
Eur J Endocrinol. 2000 Oct;143(4):543-54. doi: 10.1530/eje.0.1430543.
It has been known for many years that human benign prostatic hyperplasia (BPH) is composed predominantly of hyperplastic stromal cells rather than epithelial cells. In the present study the effects of a new steroidal aromatase inhibitor on hormone-induced and spontaneous canine BPH were investigated.
(1) Effects of TZA-2237 on hormone-induced canine BPH. Ten castrated beagles were administered testosterone and androstenedione 6 days/week for 8 months, and divided randomly into three groups after 2 months of treatment as follows. Group I served as controls, Group II was given 0.5 and Group III was given 2.5 mg/kg/day TZA-2237 5 days/week for 6 months. (2) Effects of TZA-2237 on spontaneous canine BPH. Twenty aged beagles with BPH were divided into five groups, Group IV was untreated, Group V was treated with 1 and Group VI with 5mg/kg/day TZA-2237 5 days/week for 31 weeks. Group VII was treated with 5mg/kg/day Atamestane and Group VIII was treated with 0.3 mg/kg/day chlormadinone acetate (CMA) 5 days/week. (3) Effects of TZA-2237 combined with CMA on spontaneous canine BPH. Three aged beagles with BPH were treated with 1mg/kg/day TZA-2237 and 0.03 mg/kg/day CMA 5 days/week for 20 weeks (Group IX) and a further three aged beagles with BPH were treated with 0.3 mg/kg/day CMA alone 5 days/week (Group X).
Hormone-induced prostatic growth was significantly suppressed in group III compared with that in other groups. In Group III, the intraprostatic aromatase activity, estradiol level and androgen receptor content decreased significantly in comparison with the values in Group I. The prostatic weights in Groups V, VI and VII increased significantly in comparison with the weight in Group IV. Serum LH and testosterone levels in Groups V, VI, and VII increased significantly in comparison with the level in Group IV. The prostatic weight in Group IX was decreased only slightly, but the smooth muscle component was decreased significantly.
TZA-2237 is a new, unique and effective aromatase inhibitor that causes inhibition of both epithelial and stromal compartments in hormone-induced canine BPH. Dual inhibition of androgen and estrogen resulted in inhibition of smooth muscle growth, and should prove effective as a new method of treatment given the atrophic effects on not only the epithelium but also the stroma in human BPH.
多年来已知人类良性前列腺增生（BPH）主要由增生的基质细胞而非上皮细胞组成。在本研究中，研究了一种新型甾体芳香化酶抑制剂对激素诱导的和自发性犬BPH的影响。
（1）TZA - 2237对激素诱导的犬BPH的影响。十只去势的比格犬每周6天给予睾酮和雄烯二酮，持续8个月，治疗2个月后随机分为三组，如下。第一组作为对照组，第二组给予0.5，第三组每周5天给予2.5mg/kg/天的TZA - 2237，持续6个月。（2）TZA - 2237对自发性犬BPH的影响。二十只患有BPH的老年比格犬分为五组，第四组未治疗，第五组用1mg/kg/天治疗，第六组每周5天用5mg/kg/天的TZA - 2237治疗31周。第七组用5mg/kg/天的阿那曲唑治疗，第八组每周5天用0.3mg/kg/天的醋酸氯地孕酮（CMA）治疗。（3）TZA - 2237与CMA联合对自发性犬BPH 的影响。三只患有BPH的老年比格犬每周5天用1mg/kg/天的TZA - 2237和0.03mg/kg/天的CMA治疗20周（第九组），另外三只患有BPH的老年比格犬每周仅用0.3mg/kg/天的CMA治疗5天（第十组）。
与其他组相比，第三组中激素诱导的前列腺生长受到显著抑制。在第三组中，与第一组相比，前列腺内芳香化酶活性、雌二醇水平和雄激素受体含量显著降低。与第四组相比，第五、六和七组的前列腺重量显著增加。与第四组相比，第五、六和七组的血清LH和睾酮水平显著增加。第九组的前列腺重量仅略有下降，但平滑肌成分显著减少。
TZA - 223７是一种新型、独特且有效的芳香化酶抑制剂，可抑制激素诱导的犬BPH中的上皮和基质成分。雄激素和雌激素的双重抑制导致平滑肌生长受到抑制，鉴于其对人类BPH中的上皮和基质均有萎缩作用，应证明是一种有效的新治疗方法。
