EFFECT OF PROSTATIC GROWTH FATTER, BASIC FIBROBLAST GROWTH-FACTOR, EPIDERMAL GROWTH-FACTOR, AND STEROIDS ON THE PROLIFERATION OF HUMAN FETAL PROSTATIC FIBROBLASTS

To study the relationship between androgen metabolism and the pathogen esis of benign prostatic hypertrophy, we purified a growth factor from benign hyperplastic tissue of human prostates and assayed the prolife rative responses of human fetal prostatic fibroblasts to the purified growth factor (hPGF), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), dihydrotestosterone (DHT), and estradiol (E(2)). Prostatic tissue extracts were fractionated using heparin-Sepharose c hromatography. The fraction that eluted with 1.3-1.7 M NaCl contained the majority of mitogenic activity. Sodium dodecyl sulfate polyacrylam ide gel electrophoresis (SDS/PAGE) of the lyophilyzed active fraction showed a band at 17,000 daltons. Human prostatic fibroblasts were isol ated from fetal prostate and tested for their proliferative responses to hPGF, bFGF, EGF, DHT, and E(2). hPGF, as well as bFGF and;EGF, did increase tritiated thymidine incorporation into the cultured fibroblas ts. DHT(10(-7) M) had a significant stimulatory effect on cell growth in serum-free media after 6 days of culture. E(2)(10(-7) M) had no eff ect on fell proliferation. The combination of DHT and E(2) showed no s ynergistic effect. We conclude that our purified hPGF, bFGF, and EGF p romote cell growth directly, DHT indirectly, while E(2) does not. The effect of DI-IT appears to be mediated via the increased production an d/or secretion of growth factor(s). Possibly, the bFGF-like hPGF purif ied from human benign hyperplastic prostatic tissue is such a mediator . (C) 1996 Wiley-Liss, Inc.