Influence of hormone application by subcutaneous injections or steroid-containing silastic implants on human benign...

To study the influence of androgens and estrogens on human benign prostatic hyperplasia (BPH) tissue, BPH fragments were grafted subcutaneously (s.c.) into male nude mice. Testosterone alone (group I) or in combination with 17 beta-estradiol (group III) were administered either by s.c. injections as oil suspensions or continuously by s.c. implanted steroid-containing Silastic implants (groups II and IV). Intact mice without transplants and treatment served as a control (group V). After 4 weeks of treatment, animals were exsanguinated, transplants were removed, and serum was obtained. Ninety-six percent of the BPH fragments were located; they displayed histologically typical BPH acini and stroma. In transplants of all treatment groups, the majority of secretory, as well as basal, cells displayed a proliferation comparable to the original tissue. In glandular cells of all transplants, prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) could be demonstrated immunohistochemically. Specimens removed from animals bearing testosterone implants displayed a very well preserved ultrastructure that was found less frequently in samples from injection-treated animals. Acini-bearing metaplastic epithelium were more often present in transplants treated by steroid injections and seemed to be due to lower androgen or higher estrogen serum levels. Endogenous serum testosterone levels (ng/ml +/- SD; n) were lower and more variable (i.e., higher standard deviation) in groups treated by injections (group I: 3.68 +/- 2.12; n = 5 and group III: 3.86 +/- 1.13; n = 5) and were similar to those seen in intact controls (3.93 +/- 1.62; n = 6) compared with groups treated by Silastic implants (group II: 5.11 +/- 1.14; n = 10 and group IV: 10.20 +/- 0.52; n = 4). These results indicate that by application of steroids via Silastic implants, reproducible hormone effects can be obtained on BPH tissue transplanted into male nude mice, thus providing a reliable new model system for study.