Abstract
The 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. The staining was positive in the cytoplasm but not in the nuclei. No fibro-muscular stromal cells were stained. In the glandular epithelial cells, the secretory granules were lined up along the apical plasma membrane, and exocytosis was frequently seen. In groups 2 to 4, CMA produced marked atrophy of the glandular epithelium. The interacinar fibro-muscular stroma was prominent. The intensity of the nuclear staining for AR in both epithelial and stromal cells was negative or very weak. Furthermore, the immunoreaction for 5 alpha-reductase type I in most glandular epithelial cells was negative or very weak. Ultrastructurally, the cytoplasm of the glandular epithelial cells was electron-lucent and contained relatively few, poorly developed organelles. In addition, the secretory granules were markedly decreased in both number and size. Furthermore, mitochondrial alterations such as swollen or disappeared mitochondrial cristae or decreased electron density of the matrix were frequently seen in the smooth muscle cells. 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. The atrophy after treatment with CMA may be due to shrinkage of both glandular and stromal compartments in the prostate tissue.
