Light-microscopic stereologic analysis of spontaneous and steroid-induced canine prostatic hyperplasia.

A combined light-microscopic and stereologic analysis of the canine prostate was performed under the following experimental conditions: intact and castrated dogs, spontaneous benign prostatic hyperplasia, intact and castrated dogs after treatment with testosterone, 5 alpha-dihydrotestosterone or 3 alpha-androstanediol in combination with estradiol. Regarding the absolute amounts of the glandular and stromal parts of the prostate as well as the glandular cells, no difference was found among the testosterone, 3 alpha-androstanediol and 5 alpha-dihydrotestosterone treated castrated dogs. Treatment with 5 alpha-dihydrotestosterone or 3 alpha-androstanediol in combination with 17 beta-estradiol induced a four-fold increase in glandular and a two-fold increase in stromal tissue. The glandular to stromal tissue ratio equals that found in spontaneous canine hyperplasia, which is indicative of the glandular type of spontaneous canine hyperplasia. Therefore, it can be stated that treatment with 5 alpha-dihydrotestosterone or 3 alpha-androstanediol combined with 17 beta-estradiol not only induces prostatic overgrowth but also leads to prostatic hyperplasia of the glandular type. However, the stereologic analysis of canine prostates following steroid administration shows that canine hyperplasia is primarily a glandular disease, while human benign prostatic hyperplasia shows more stromal activation.

Androgen and estrogen effect on guinea pig seminal vesicle muscle: a combined stereological and biochemical study.

A combined electron microscopic stereological and biochemical study of the smooth muscle cells of guinea pig seminal vesicles was performed in intact, castrated, castrated and dihydrotestosterone- or estradiol-treated adult animals. Castration led to cell atrophy as determined stereologically by a decreased single cell volume and biochemically by no change in DNA content coupled with an increase in the DNA concentration. Treatment of castrates with dihydrotestosterone restored both the stereological and biochemical parameters of the cell size to slightly supranormal levels. The estrogen-induced increase in muscle weight and DNA content appeared to be due only to hyperplasia of muscle cells and not to a proliferation of fibroblasts or to infiltration by inflammatory cells. In all treatment groups, including the estrogen-treated castrates, more than 95% of the cells in the tissue were smooth muscle cells, and there was no evidence that polyploidy contributed to changes in DNA levels. In addition, in the estrogen-treated muscles, DNA concentration remained high, and the stereologically determined cell size remained low. Therefore, both morphological and biochemical evidence indicate that androgen induces hypertrophy, whereas estrogen induces hyperplasia of muscle cells. The correction of stereological and biochemical data validates the application of stereological cell size determination for smooth muscle cells in organs that hardly can be separated into stromal and epithelial components; eg, the prostate.

Human skin grafts on nude athymic mice: a light microscopic stereological study.

A morphometric procedure is presented, which allows quantitative information to be obtained from the epidermis at the light microscope level. The application of this procedure to human skin grafted to the nude mouse revealed acanthosis of the grafted epidermis compared to the original donor skin. All epidermal layers were thicker, but the increase in the granular layer was especially marked. The ratio of the basement membrane surface to the epithelial surface showed no significant change. A possible explanation for the acanthosis of the graft might be the higher mechanical stress on the nude mouse compared to the original site on the abdomen. This adaptation of the grafted epidermis does not limit the usefulness of this animal model for dermatological research, when it is assessed by objective methods, allowing statistical comparison as described here.

Smooth muscle cell of the canine prostate in spontaneous benign hyperplasia, steroid induced hyperplasia and estrogen or tamoxifen treated dogs.

Human benign prostatic hyperplasia is a predominantly stromal hyperplasia with accumulation of connective tissue. The main ultrastructural finding, which may be causal, is an activation of the smooth muscle cells, as seen by an increase of the volume density of the organelles within these cells. The dog is widely used as an animal model for human prostatic hyperplasia in spite of several differences. In this work the smooth muscle cells of the spontaneous and steroid-induced (by treating castrates with dihydrotestosterone and estradiol) prostatic hyperplasia of dogs were analysed by electron microscopical morphometry, and compared to estrogen or tamoxifen (antiestrogen) treated dogs as well as to untreated or castrated control dogs. The results clearly show that the prostatic smooth muscle cells of the dog can be activated by estrogen as well as tamoxifen, which proves the estrogenic side activity of the latter. In marked contrast to that, neither in the spontaneous nor in the steroid-induced prostatic hyperplasia could an activation of the smooth muscle cells be found. This is a most important difference from human benign prostatic hyperplasia, which limits the use of this animal model, and it might even be the explanation of the different reaction of human and canine prostatic hyperplasia to therapeutic hormonal manipulations.