Murakoshi M, Tagawa M, Inada R, Suzuki M, Mizokami A, Watanabe K
Safety Research Department, Teikoku Hormone Mfg. Co. Ltd., Kawasaki, Japan.
Endocr J. 1993 Aug;40(4):479-88. doi: 10.1507/endocrj.40.479.
The effect of a synthetic steroidal anti-androgen, TZP-4238, on steroid-induced rat prostatic hyperplasia was investigated. Male Wistar rats were divided into four experimental groups. Group 1 consisted of intact controls. The other animals were castrated. The castrated animals were treated for 7 weeks with 1) testosterone 1 mg/head plus 17 beta-estradiol (E2) 0.01 mg/head (Group 2), 2) testosterone plus E2 + TZP-4238 8 mg/kg (Group 3) and 3) testosterone plus E2 + chlormadinone acetate (CMA) 20 mg/kg (Group 4). TZP-4238 and CMA were administered orally for 4 weeks after 3 weeks treatment with testosterone plus E2. In group 2, glandular hyperplasia of the prostate was clearly observed, and the number of bromo-deoxyuridine (BrdU)-positive cells showed a significant increase. In contrast, combined treatment with TZP-4238 (Group 3) or CMA (Group 4) produced marked atrophy of the glandular epithelium, and the number of BrdU-positive cells were remarkably decreased compared with Group 2. In addition, the localization of glutathione-peroxidase (GSH-PO) which effectively reduces the lipid peroxides in the glandular epithelial cells was markedly decreased. Furthermore, nuclear immunostaining of androgen receptor was remarkably decreased after combined treatment with TZP-4238 or CMA. Our data indicate that TZP-4238 is a potent steroidal androgen receptor antagonist for the prevention of rat prostatic growth in the steroid-induced prostatic hyperplasia model.
研究了合成甾体抗雄激素TZP - 4238对类固醇诱导的大鼠前列腺增生的影响。雄性Wistar大鼠分为四个实验组。第1组为完整对照组。其他动物进行去势。去势动物用以下药物治疗7周：1）睾酮1mg/只加17β - 雌二醇（E2）0.01mg/只（第2组），2）睾酮加E2加TZP - 4238 8mg/kg（第3组），3）睾酮加E2加醋酸氯地孕酮（CMA）20mg/kg（第4组）。在用睾酮加E2治疗3周后，口服TZP - 4238和CMA 4周。在第2组中，明显观察到前列腺的腺体增生，且溴脱氧尿苷（BrdU）阳性细胞数量显著增加。相比之下，TZP - 4238（第3组）或CMA（第4组）联合治疗导致腺体上皮明显萎缩，与第2组相比，BrdU阳性细胞数量显著减少。此外，有效减少腺上皮细胞中脂质过氧化物的谷胱甘肽过氧化物酶（GSH - PO）的定位明显降低。此外，TZP - 4238或CMA联合治疗后雄激素受体的核免疫染色显著降低。我们的数据表明，在类固醇诱导的前列腺增生模型中，TZP - 4238是一种有效的甾体雄激素受体拮抗剂，可预防大鼠前列腺生长。
