Murakoshi M, Inada R, Makino M, Suzuki M, Mieda M, Honma S, Yamanaka H
Department of Safety Research, Teikoku Hormone Mfg. Co. Ltd., Kawasaki, Japan.
Acta Pathol Jpn. 1990 Dec;40(12):871-9. doi: 10.1111/j.1440-1827.1990.tb03332.x.
The effect of a synthetic steroidal anti-androgen, TZP-4238, on steroid-induced canine prostatic hyperplasia was studied by light and electron microscopy. Male beagle dogs (1-2 years old) were divided into four experimental groups. Group 1 consisted of intact controls. The other animals were castrated. The castrated animals were treated for 25 weeks with 1) 5 alpha-androstane-3 alpha, 17 beta-diol (A-diol) plus 17 beta-estradiol (E2) (Group 2), 2) A-diol plus E2 + TZP-4238 0.5 mg/kg (Group 3) and 3) A-diol plus E2 + chlormadinone acetate (CMA) 2.5 mg/kg (Group 4). TZP-4238 and CMA were administered orally for 21 weeks after 4 weeks treatment with A-diol plus E2. In group 2, glandular hyperplasia of the prostate was clearly noted. In contrast, combined treatment with TZP-4238 (Group 3) or CMA (Group 4) produced marked atrophy of the glandular epithelium. Loss of secretory and metabolic activities was confirmed by ultrastructural investigations. Our data indicate that TZP-4238 is a potent anti-androgen for the prevention of canine prostatic hyperplasia in the steroid-induced benign prostatic hyperplasia (BPH) model.
通过光学显微镜和电子显微镜研究了合成甾体抗雄激素TZP-4238对类固醇诱导的犬前列腺增生的影响。将雄性比格犬（1-2岁）分为四个实验组。第1组为完整对照组。其他动物进行了去势。对去势动物进行25周的治疗，治疗方案如下：1）5α-雄甾烷-3α,17β-二醇（A-二醇）加17β-雌二醇（E2）（第2组）；2）A-二醇加E2加0.5mg/kg的TZP-4238（第3组）；3）A-二醇加E2加2.5mg/kg的醋酸氯地孕酮（CMA）（第4组）。在用A-二醇加E2治疗4周后，将TZP-4238和CMA口服给药21周。在第2组中，明显观察到前列腺的腺体增生。相比之下，TZP-4238（第3组）或CMA（第4组）联合治疗导致腺上皮明显萎缩。超微结构研究证实了分泌和代谢活性的丧失。我们的数据表明，在类固醇诱导的良性前列腺增生（BPH）模型中，TZP-4238是预防犬前列腺增生的有效抗雄激素。
