Multiple phenotypes of prostatic glandular cells in castrated dogs after individual or combined treatment with androgen and estrogen. Morphometric, ultrastructural, and cytochemical distinctions.

Abstract

To demonstrate a potential for multidirectional differentiation in mature prostatic epithelium, 17 beta-estradiol 17-cyclopentylpropionate (ECP) and 5 alpha-androstane-3 alpha, 17 beta-diol dipropionate (3 alpha-diol DP) were administered individually and in combination to castrated dogs. Quantitative ultrastructural and cytochemical methods were used to distinguish phenotypes of glandular cells in the various hormonal environments. Castration-induced glandular cell regression was accompanied by an increased nuclear to cytoplasmic ratio; by enhanced keratin positivity, expressed as dispersed immunolabeled tonofilaments; and by an absence of peanut agglutinin (PNA) binding sites on luminal membranes. Administration of ECP resulted in squamous metaplasia as well as hypertrophy of the glandular epithelium. The hypertrophied estrogen-modified glandular (EMG) cells were characterized by a new population of small (0.29 micron in diameter) secretory granules, bundles of tonofilaments, and PNA-positive luminal membranes. Treatment of castrated dogs with 3 alpha-diol DP produced a greater epithelial hypertrophy than ECP. These cells were characterized by larger (0.49 micron in diameter) secretory granules, dispersed tonofilaments, and no detectable PNA receptors. Joint administration of ECP and 3 alpha-diol DP caused a florid response including squamous metaplasia and hypertrophy of the glandular epithelium which was associated with the emergence of a novel phenotype in androgen-estrogen modified glandular (A-EMG) cells. In A-EMG cells, secretory granules were similar in size to those found in 3 alpha-diol DP-dominated epithelium whereas tonofilaments often appeared in bundles and luminal membranes were PNA positive, i.e., features found in EMG cells. Our results indicate that atrophic canine prostatic glandular cells possess pluripotentiality of response to sex hormones.