Effects of the new steroidal antiandrogen TZP-4238 on hormone-induced canine prostatic hyperplasia.
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.
D015113:Androstane-3,17-diol / Q000032:analysis; D000818:Animals; D002715:Chlormadinone Acetate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D042944:Cholestenone 5 alpha-Reductase; D013196:Dihydrotestosterone / Q000032:analysis; D004285:Dogs; D008297:Male; D009929:Organ Size; D010088:Oxidoreductases / Q000032:analysis; D011467:Prostate / Q000737:chemistry / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D011944:Receptors, Androgen / Q000032:analysis; D014463:Ultrasonography
D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D002715:Chlormadinone Acetate; D015113:Androstane-3,17-diol; D010088:Oxidoreductases; D042944:Cholestenone 5 alpha-Reductase; C069297:osaterone acetate