No abstract

Hormonal manipulation of intact male baboons has produced prostatic features resembling benign prostatic hypertrophy (BPH) in man. Long-acting androgen, testosterone enanthate (TE), given weekly (200 mg i.m.) for up to six months, caused significant gravimetric and volumetric increases in the prostate; a definite glandular and marked stromal hyperplasia with fibrosis developed in the caudal lobe (CD). After twenty weeks of TE treatment, there were dysplastic (atypical) changes in the glandular lining epithelium in the CD, causing pseudostratification of the lining cells with nuclear hyperchromatism. By the twenty-eighth week, there was an increase of stromal tissue with papillary ingrowth or invagination of glandular epithelium in the CD. Serum levels of testosterone and dihydrotestosterone were significantly elevated from 10 nm/ml and 2-3 ng/ml to 30-40 ng/ml and 5-6 ng/ml, respectively. There was a 3 to 4-fold increase in androstenedione levels and an increase in estradiol-17 beta from 20 pg/ml to 80-90 pg/ml. These steroidal levels may have played a direct role in the induction of early BPH in the baboons. Cytoplasmic and nuclear androgen receptor levels were higher in the CD compared to those of the cranial lobe (CR); AR concentration was increased in the cytosol and decreased in the nuclei of both lobes in TE treated animals. Scanning and transmission electron microscopy revealed heavy deposition of collagen fibers (fibrosis) in the central and periurethral regions of the CD after the administration of TE. Glandular as well as epithelial hyperplasia was most notable in the peripheral zone of the CD. These findings are similar to observations established in human BPH, indicating that the baboon prostate may be a useful model for studying various parameters of BPH.

Cytosol receptors for estrogens (ER) and progestins (PR) were assayed in human prostatic carcinoma (CaP) and benign prostatic hyperplasia (BPH). Specimens were obtained from either the peripheral or the periurethral zone of the prostate. Stringent criteria were used to identify and measure 7‐8S specific receptor using sucrose gradient analysis in a vertical tube rotor. Progesterone receptor was found in 14 BPH samples assayed and in 12 of 13 prostate cancers. In contrast, the 7‐8S estrogen receptor was found in none of the nine benign samples assayed and in all prostate cancers. BPH samples were taken from either peripheral or periurethral zones and gave similar results. The histology of individual specimens did not correlate with either the ER or PR present, and, in the cancers, there was no correlation between the pathologic stage or the Gleason score and receptor content.

Specific receptors for dihydrotestosterone and estradiol-17-beta have been identified in cytosols of the human and baboon prostate. Binding of radioactive estradiol-17-beta to the 0.4 M potassium chloride extractable component of human prostate nuclei also was demonstrated. Cyproterone acetate and diethylstilbestrol, agents of known high affinity for dihydrotestosterone and estradiol-17-beta receptors, respectively, did not bind significantly to sex hormone binding globulin and, therefore, were useful as competitors in distinguishing binding of dihydrotestosterone and estradiol-17-beta to sex hormone binding globulin and to their specific receptors. Displacement of [3H]-estradiol-17-beta binding by diethylstilbestrol in cytosols of 11 needle biopsy specimens (mean equals 16.8 mg.) from prostatic cancer patients was analyzed. These preliminary data indicated a trend towards greater competition by diethylstilbestrol for high affinity binding sites in differentiated tumor specimens from men who were not receiving estrogen therapy. Objective and subjective responses to hormone therapy were recorded in these patients, whereas the disease in those men with low displacement assay values progressed.

No abstract