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.
Geller
J
J
Mercy Hospital and Medical Center, San Diego, CA 92103.
Sionit
L R
LR
Baird
A
A
Kohls
M
M
Connors
K M
KM
Hoffman
R M
RM
D000726:Androgen Antagonists / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D046508:Culture Techniques; D013196:Dihydrotestosterone / Q000378:metabolism* / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000032:analysis*; D005485:Flutamide / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D008297:Male; D008535:Megestrol / Q000031:analogs & derivatives; D019290:Megestrol Acetate; D009919:Orchiectomy / Q000379:methods; D011467:Prostate / Q000737:chemistry / Q000187:drug effects* / Q000254:growth & development; D011470:Prostatic Hyperplasia / Q000473:pathology / Q000503:physiopathology*; D011863:Radioimmunoassay
D000726:Androgen Antagonists; D013196:Dihydrotestosterone; D016222:Fibroblast Growth Factor 2; C014290:hydroxyflutamide; D005485:Flutamide; D008535:Megestrol; D019290:Megestrol Acetate