Inhibition of steroid-induced prostatic hyperplasia in rats by treatment with anti-androgen (TZP-4238).

Inhibition of steroid-induced prostatic hyperplasia in rats by treatment with anti-androgen (TZP-4238).
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通过抗雄激素 (TZP-4238) 治疗抑制大鼠类固醇诱导的前列腺增生。

DOI:
10.1507/endocrj.40.479
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发表时间:
1993
期刊:
影响因子:
2
通讯作者:
K. Watanabe
K. Watanabe
中科院分区:
医学4区
文献类型:
--
作者:
M. Murakoshi;M. Tagawa;R. Inada;M. Suzuki;A. Mizokami;K. Watanabe

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研究了合成的甾体抗雄激素TZP-4238对甾体诱导的大鼠前列腺增生的作用。雄性Wistar大鼠分为4个实验组。第1组为完整对照组。其他动物被阉割。去势动物用1)睾酮1 mg/头加17 β-雌二醇(E2)0.01 mg/头(组2)、2)睾酮加E2 + TZP-4238 8 mg/kg(组3)和3)睾酮加E2 +醋酸氯地孕酮(CMA)20 mg/kg(组4)处理7周。用睾酮加E2治疗3周后,口服TZP-4238和CMA 4周。在第2组中,前列腺腺体增生,清楚地观察到,溴脱氧尿苷(BrdU)阳性细胞的数量显着增加。与此相反,TZP-4238(第3组)或CMA(第4组)的联合治疗导致腺上皮显著萎缩,BrdU阳性细胞的数量与第2组相比显著减少。此外,谷胱甘肽过氧化物酶(GSH-PO),有效地减少脂质过氧化物在腺上皮细胞的定位显着减少。此外,TZP-4238或CMA联合治疗后,雄激素受体的核免疫染色显着减少。我们的数据表明,TZP-4238是一种有效的甾体雄激素受体拮抗剂,用于预防类固醇诱导的前列腺增生模型中的大鼠前列腺生长。
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.
DOI: 10.1210/endo-127-6-3180
发表时间: 1990-12-01
期刊: ENDOCRINOLOGY
影响因子: 4.8
作者:
SAR, M;LUBAHN, DB;WILSON, EM
通讯作者: WILSON, EM
DOI: 10.1210/mend-2-12-1276
发表时间: 1988-12
影响因子: --
作者:
Jiann-an Tan;D. R. Joseph;V. Quarmby;D. Lubahn;M. Sar;F. S. French;E. M. Wilson
通讯作者: Jiann-an Tan;D. R. Joseph;V. Quarmby;D. Lubahn;M. Sar;F. S. French;E. M. Wilson