Induction of benign prostatic hypertrophy in baboons.

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.