Takezawa Y, Fukabori Y, Yamanaka H, Mieda M, Honma S, Kushitani M, Hamataki N
Department of Urology, Gunma University School of Medicine, Japan.
Prostate. 1992;21(4):315-29. doi: 10.1002/pros.2990210408.
The effects of the new steroidal antiandrogen TZP-4238 on hormone-induced canine prostatic hyperplasia (BPH) were studied in comparison with those of chlormadinone acetate (CMA), a steroidal antiandrogen used in Japan. One- to 2-year-old beagle dogs were castrated and administered 75 mg/week of androstanediol (A-diol) plus 0.75 mg/week of estradiol (E2) for 25 weeks. These dogs were treated orally with placebo, 0.5 mg/kg/day of TZP-4238, 0.1 mg/kg/day of TZP-4238, and 2.5 mg/kg/day of CMA, respectively, for 21 weeks after 4 weeks treatment with A-diol plus E2. Treatment with 0.5 mg/kg/day of TZP-4238 or 2.5 mg/kg/day of CMA suppressed prostatic growth, and treatment with 0.1 mg/kg/day of TZP-4238 suppressed prostatic growth slightly. Treatment with 0.5 mg/kg/day of TZP-4238 decreased 5 alpha-reductase activity, DHT content, and nuclear androgen receptor (AR) content in the prostate, and treatment with 0.1 mg/kg/day of TZP-4238 or 2.5 mg/kg/day of CMA also decreased or tended to decrease these parameters. In conclusion, TZP-4238 and CMA were effective in inhibiting the growth of hormone-induced canine BPH, and TZP-4238 was at least 5 times more potent than CMA. TZP-4238 inhibited prostatic growth by decreasing prostatic androgen content and the androgen-AR complex. TZP-4238 decreased 5 alpha-reductase activity by prevention of the androgen action described above.
将新型甾体类抗雄激素药物TZP - 4238与日本使用的甾体类抗雄激素药物醋酸氯地孕酮（CMA）相比较，研究了其对激素诱导的犬前列腺增生（BPH）的影响。选用1至2岁的比格犬，对其进行去势手术，并给予每周75mg的雄烷二醇（A - 二醇）加每周0.75mg的雌二醇（E2），持续25周。在给予A - 二醇加E2治疗4周后，这些犬分别口服安慰剂、每天0.5mg/kg的TZP - 4238、每天0.1mg/kg的TZP - 4238和每天2.5mg/kg的CMA，持续21周。每天0.5mg/kg的TZP - 4238或每天2.5mg/kg的CMA治疗可抑制前列腺生长，每天0.1mg/kg的TZP - 4238治疗可轻微抑制前列腺生长。每天0.5mg/kg的TZP - 4238治疗可降低前列腺中5α - 还原酶活性、双氢睾酮（DHT）含量和核雄激素受体（AR）含量，每天0.1mg/kg的TZP - 4238或每天2.5mg/kg的CMA治疗也可降低或趋于降低这些参数。总之，TZP - 4238和CMA均可有效抑制激素诱导的犬BPH生长，且TZP - 4238的效力至少是CMA的5倍。TZP - 4238通过降低前列腺雄激素含量和雄激素 - AR复合物来抑制前列腺生长。TZP - 4238通过阻止上述雄激素作用来降低5α - 还原酶活性。
