INFLUENCE OF HORMONE APPLICATION BY SUBCUTANEOUS INJECTIONS OR STEROID-CONTAINING SILASTIC IMPLANTS ON HUMAN BENIGN HYPERPLASTIC PROSTATE TISSUE TRANSPLANTED INTO MALE NUDE-MICE

To study the influence of androgens and estrogens on human benign pros tatic hyperplasia (BPH) tissue, BPH fragments were grafted subcutaneou sly (s.c.) into male nude mice. Testosterone alone (group I) or in com bination with 17beta-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 w ithout transplants and treatment served as a control (group V). After 4 weeks of treatment, animals were exsanguinated, transplants were rem oved, and serum was obtained. Ninety-six percent of the BPH fragments were located; they displayed histologically typical BPH acini and stro ma. In transplants of all treatment groups, the majority of secretory, as well as basal, cells displayed a proliferation comparable to the o riginal tissue. In glandular cells of all transplants, prostate-specif ic antigen (PSA) and prostatic acid phosphatase (PAP) could be demonst rated immunohistochemically. Specimens removed from animals bearing te stosterone implants displayed a very well preserved ultrastructure tha t was found less frequently in samples from injection-treated animals. Acini-bearing metaplastic epithelium were more often present in trans plants treated by steroid injections and seemed to be due to lower and rogen or higher estrogen serum levels. Endogenous serum testosterone l evels (ng/ml +/- SD; n) were lower and more variable (i.e., higher sta ndard 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 tho se 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 gro up IV: 10.20 +/- 0.52; n = 4). These results indicate that by applicat ion of steroids via Silastic implants, reproducible hormone effects ca n be obtained on BPH tissue transplanted into male nude mice, thus pro viding a reliable new model system for study.