Effects of a new steroidal antiandrogen, TZP-4238 (17 alpha-acetoxy-6-chloro-2-oxa-4, 6-pregnadiene-3, 20-dione), on spontaneously developed canine benign prostatic hyperplasia.
The effects of the new steroidal antiandrogen, TZP-4238 on spontaneously-developed canine prostatic hyperplasia (BPH) were studied in comparison with those of chlormadinone acetate (CMA), a steroidal antiandrogen used for the treatment of BPH and prostatic cancer in Japan. Aged beagle dogs (5-9 years old) with spontaneously developed BPH (mean prostate volume, 17.7ml) were treated orally with a placebo, TZP-4238 (0.1 mg/kg/day, 0.01 mg/kg/day), or CMA (3 mg/kg/day), for 25 weeks. Prostate volume was measured by transrectal ultrasonography before treatment and every 5 weeks during treatment. TZP-4238 produced a regression in spontaneously developed canine BPH, its effects being more potent than those of CMA. TZP-4238 reduced the content of testosterone, dihydrotestosterone (DHT) and androgen receptor in the prostates of these animals, suggesting antiandrogenic mechanisms of the agent. TZP-4238 also appeared to reduce 5 alpha-reductase activity by prevention of the androgen action in prostate as described above.
Takezawa
Y
Y
Department of Urology, Gunma University School of Medicine, Maebashi, Japan.
Ito
K
K
Suzuki
K
K
Fukabori
Y
Y
Yamanaka
H
H
Honma
S
S
Mieda
M
M
Hamataki
N
N
Kushitani
M
M
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000032:analysis / Q000378:metabolism; D000726:Androgen Antagonists / Q000592:standards / Q000627:therapeutic use*; D000818:Animals; D002715:Chlormadinone Acetate / Q000031:analogs & derivatives* / Q000592:standards / Q000627:therapeutic use; D003276:Contraceptives, Oral / Q000592:standards / Q000627:therapeutic use; D013196:Dihydrotestosterone / Q000032:analysis / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D008297:Male; D009929:Organ Size; D011467:Prostate / Q000737:chemistry / Q000000981:diagnostic imaging / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000473:pathology; D011944:Receptors, Androgen / Q000032:analysis / Q000378:metabolism; D013739:Testosterone / Q000032:analysis / Q000097:blood / Q000378:metabolism; D014463:Ultrasonography
D000726:Androgen Antagonists; D003276:Contraceptives, Oral; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D002715:Chlormadinone Acetate; D013739:Testosterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C069297:osaterone acetate