Inhibitory influence of a new steroidal anti-androgen, TZP-4238, on prostatic hyperplasia in the beagle dog.
The effect of a synthetic steroidal anti-androgen, TZP-4238, on spontaneous benign prostatic hyperplasia (BPH) in dogs was investigated. Old male beagle dogs (5-9 years old) were divided into three experimental groups. Group 1 consisted of BPH controls. Groups 2 and 3 received TZP-4238 0.1 mg/kg/day and chlormadinone acetate (CMA) 0.3 mg/kg/day p.o., respectively, for 5 months. In group 1, glandular hyperplasia of the prostate was clearly detected. In contrast, TZP-4238 (Group 2) or CMA (Group 3) produced marked atrophy of the glandular epithelium. In addition, a histopathological study showed that TZP-4238 or CMA medication for 5 months exerted no effect on the testes and the pituitary luteinizing hormone (LH) cells. Therefore, it is suggested that TZP-4238 (0.1 mg/kg) or CMA (0.3 mg/kg) causes regression of spontaneous canine BPH without any histopathological effects on the testes and pituitary LH cells. However, slightly decreased serum testosterone levels were found in TZP-4238-treated animals, due apparently to a direct and/or indirect effect on the testes. Thus, it is suggested that a marginal antigonadotrophic effect cannot be excluded. It is concluded that TZP-4238 is a potent anti-androgen for the treatment of spontaneous canine BPH, without any negative influence on the function of the testes and the pituitary LH cells.
Murakoshi
M
M
Department of Safety Research, Teikoku Hormone Mfg. Co. Ltd., Kawasaki, Japan.
Inada
R
R
Tagawa
M
M
Makino
M
M
Suzuki
M
M
Mieda
M
M
Honma
S
S
Takezawa
Y
Y
Yamanaka
H
H
D000818:Animals; D002715:Chlormadinone Acetate / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004285:Dogs; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010902:Pituitary Gland / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D013737:Testis / Q000473:pathology; D013739:Testosterone / Q000097:blood
D002715:Chlormadinone Acetate; D013739:Testosterone; C069297:osaterone acetate