Abstract: | Histologic specimens of ventral and dorsolateral prostate from ACI male rats of varying ages (3, 6, 12, 18, 24, and 29–32 months) were examined to identify changes associated with the development of adenocarcinoma. The same specimens were examined immunohistochemically for their distribution of prolactin binding sites. At 3 months of age ventral lobes of these ACI rats exhibited normal histology and prolactin binding patterns. At 6 and 12 months of age most ventral prostate alveoli showed epithelial cell atrophy, along with occasional acini containing normal-looking epithelial cells. Prolactin binding activity was present in most epithelial cells at 6 months of age but disappeared from atrophied cells at 12 months of age. At 18 months of age epithelial atrophy was more advanced and devoid of prolactin binding activity while zones of epithelial cell proliferation were expanded containing populations of normal-looking cells, and cells that were either hyperplastic or dysplastic (abnormal looking), all of which were capable of binding prolactin. Older rats, 24–32 months of age, also showed prostatic adenocarcinoma in ventral prostate and these cancerous cells bound prolactin. A continuum was frequently seen between areas of normal epithelial cells, hyperplasia, dysplasia, and adenocarcinoma of ventral prostate. Morphology and prolactin binding patterns in dorsal and lateral prostates of old ACI rats were similar to young adult rats and did not contain adenocarcinoma. In conclusion, age-dependent atrophy of the ventral prostate gland of ACI rats occurs early in life and precedes adenocarcinoma. Precancerous dysplastic changes appear to arise from normal and hyperplastic epithelial cells that are capable of binding prolactin rather than those that undergo precocious atrophy and lose their prolactin binding activity. Although atrophic epithelial cells do not appear to be progenitors of prostatic cancer, the possible relationship between precocious senescence (atrophy) and adenocarcinoma in ventral prostates of ACI rats is discussed. |