Androgen responsiveness of stromal cells of the human prostate: regulation of cell proliferation and keratinocyte growth factor by androgen.
OBJECTIVE
Growth and development of the prostate are androgen dependent and mainly influenced by stromal-epithelial interaction. It is believed that indirect androgenic activation of paracrine factors like keratinocyte growth factor (KGF) in the prostatic stroma influences the growth of epithelial cells. In this study we investigated the role androgen plays in stromal cell growth and stimulation of KGF in the human prostate.


METHODS
Stromal cells were derived from explant primary culture of human normal or benign prostatic tissue. The effect of different dihydrotestosterone (DHT) concentrations on cell proliferation was measured using 3[H]thymidine incorporation assay. The effect of DHT on levels of KGF protein was determined by Western blotting. The effect of DHT on levels of KGF gene expression was measured by various cycles of polymerase-chain-reaction (PCR) and multiplex PCR.


RESULTS
Characterization of stromal cells showed epithelial cells less than 9.5% in all passages. DHT stimulated human prostate stromal cells in a dose dependent fashion over a concentration range of 0.001-10 nM. Immunocytochemical evaluation of KGF after DHT exposure showed a higher staining intensity. Relative quantitation of Western blotting showed a 1.93-fold increase in KGF protein in the androgen treated stromal cells. At 1 nM DHT conventional and multiplex PCR revealed a significant stimulation of the KGF mRNA expression.


CONCLUSIONS
These data show for the first time that androgen stimulates cell proliferation as well as KGF protein and gene expression in human prostate stromal cells. This supports the hypothesis that androgen-induced stromal-derived KGF stimulates prostate epithelial cell growth.
Planz
B
B
Department of Urology, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
Wang
Q
Q
Kirley
S D
SD
Lin
C W
CW
McDougal
W S
WS
D000368:Aged; D000728:Androgens / Q000502:physiology*; D002455:Cell Division; D002478:Cells, Cultured; D003470:Culture Media; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D006133:Growth Substances / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D015603:Keratinocytes; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000166:cytology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D017154:Stromal Cells
D000728:Androgens; D003470:Culture Media; C496453:FGF7 protein, human; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D012333:RNA, Messenger; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors