Atrophic effects of antiandrogen, chlormadinone acetate (CMA) on dog prostate with spontaneous benign prostatic hyperplasia.
The atrophic effect of a synthetic steroidal antiandrogen, chlormadinone acetate (CMA), on spontaneous benign prostatic hyperplasia (BPH) in dogs was investigated. Male beagle dogs (5-8 years old) were divided into four experimental groups. Group 1 consisted of untreated controls. Groups 2 to 4 received CMA 0.03, 0.1, and 0.3 mg/kg/day, p.o., respectively, for 6 months. In group 1, glandular hyperplasia of the prostate was clearly detected. The glandular epithelial cells showed uniformly intense nuclear staining for androgen receptor (AR). AR was also localized in the nuclei of the fibro-muscular stromal cells. Immunoreactivity of 5 alpha-reductase type I was positive in most glandular epithelial cells. No fibro-muscular stromal cells were stained. Immunolocalization of 5 alpha-reductase type II was clearly detected in the interacinar fibro-muscular stromal cells, but not in the glandular epithelial cells. In groups 2 to 4, CMA produced marked atrophy of the glandular epithelium. The interacinar fibro-muscular stroma was prominent. The nuclear staining for AR in both epithelial and stromal cells was remarkably decreased. Furthermore, the immunoreaction for 5 alpha-reductase type I in most glandular epithelial cells was negative or very weak. The immunoreaction of 5 alpha-reductase type II in the interacinar fibro-muscular stromal cells was negative or very weak. These results indicate that the uptake of testosterone and/or its androgenic effect on the prostate may be suppressed by CMA. The decreased AR-immunostaining may be explained by the decrease in the number of AR and/or antibody binding sites for AR. Therefore, the atrophy after treatment with CMA may be due to shrinkage of both glandular and stromal compartments in the prostate tissue.
Murakoshi
M
M
Safety Research Department, Teikoku Hormone Mfg. Co., Ltd., Kanagawa, Japan.
Tagawa
M
M
Ikeda
R
R
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D000726:Androgen Antagonists / Q000633:toxicity*; D000818:Animals; D001284:Atrophy / Q000139:chemically induced; D002715:Chlormadinone Acetate / Q000633:toxicity*; D004285:Dogs; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000201:enzymology / Q000473:pathology*; D011470:Prostatic Hyperplasia / Q000201:enzymology / Q000473:pathology*; D011944:Receptors, Androgen / Q000378:metabolism
D000726:Androgen Antagonists; D007527:Isoenzymes; D011944:Receptors, Androgen; D002715:Chlormadinone Acetate; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase