In vivo and in vitro effects of androgen on fibroblast growth factor-2 concentrations in the human prostate

Prostatic growth is primarily regulated by dihydrotestosterone (DHT). Recent studies have demonstrated that a large number of growth factors are present in the human benign prostatic hyperplasia (BPH) prostate, including epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), transforming growth factor beta (TGF-beta), insulin-like growth factor (IGF), and basic fibroblast growth factor (bFGF) (FGF-2). DHT may mediate its mitogenic effects in the prostate by regulating growth factors. To test this hypothesis, we have utilized a histoculture androgen sensitivity assay (HASA) in which 3H-thymidine incorporation is measured in aliquots of BPH tissue in histoculture with either added DHT or hydroxyflutamide (HF). The resulting DHT/HF ratio is an expression of the androgen sensitivity of the tissue. In this study, we have compared the DHT/HF ratio for 3H-thymidine incorporation to the DHT/HF ratio for FGF-2 measured in the histocultured prostates. The DHT/HF ratio for the HASA studies of 3H-thymidine incorporation averaged 2.68 compared to the DHT/HF ratio for FGF-2 in the same specimens of 1.01. These values were significantly different, therefore indicating no relationship between DHT stimulation and FGF-2 levels. In addition, FGF-2 levels were measured in human BPH prostates from patients medically castrated with megesterol acetate and estradiol 17-beta prior to surgery. These values were not significantly different, and therefore do not suggest any effect of DHT on the concentration of prostatic FGF-2. Although these studies did not show any effect of DHT on the regulation of prostatic FGF-2, they do indicate that the HASA assay is feasible and appropriate to use in the study of relationships between DHT and various growth factors.