Biochemical and histological studies on prostates in castrated dogs after treatment with androstanediol, oestradiol and cyproterone acetate.

The effect of cyproterone acetate (CA) on experimentally induced benign prostatic hyperplasia (BPH) in the castrated dog was investigated. BPH was induced by 6 months' treatment with 3 alpha-androstanediol (3 alpha-diol) alone and in combination with 17 beta-oestradiol (Oe2). RNA, DNA and zinc content of the glands were determined in addition to histological examination and measurement of the prostates. Two different types of prostatic enlargement were observed. First, 3 alpha-diol induced typical diffuse canine hyperplasia with replacement of functional activity. DNA, RNA and the zinc content of total glands were increased compared with intact controls. Second, 3 alpha-diol plus Oe2 produced on the one hand a more striking increase of prostatic weights, but on the other a loss of typical morphological structure and function. Histologically, transformation of simple glandular epithelium into stratified squamous metaplasia occurred in addition to stimulation of fibromuscular tissue. Biochemically, a relative decrease of DNA per mg tissue was measured with a fall in the RNA to DNA ratio and zinc to the values of castrates. Administration of CA resulted in an abolition of the 3 alpha-diol effect. Biochemical determinations and histological examinations revealed an effect similar to castration after treatment with 3 alpha-diol plus CA. After treatment with 3 alpha-diol plus Oe2 plus CA fibromuscular stimulation as an oestrogen effect predominated in addition to glandular atrophy and metaplastic changes, especially in prostatic ducts. Epithelial hyperplasia is an effect of 3 alpha-diol, whereas metaplastic proliferation only occurs in oestrogenized and androgenized dogs. In both types of prostatic enlargement CA prevents development of hyperplastic prostate.