Prostatic growth and development are regulated by FGF10

We have examined the role of Fibroblast Growth Factor 10 (FGF10) during the growth and development of the rat ventral prostate (VP) and seminal vesicl e (SV), FGF10 transcripts were abundant at the earliest stages of organ for mation and during neonatal organ growth, but were low or absent in growth-q uiescent adult organs. In both the VP and SV, FGF10 transcripts were expres sed only in a subset of mesenchymal cells and in a pattern consistent with a role as a paracrine epithelial regulator. In the neonatal VP, FGF10 mRNA was expressed initially in mesenchymal cells peripheral to the peri-urethra l mesenchyme and distal to the elongating prostatic epithelial buds, At lat er stages, mesenchymal cells surrounding the epithelial buds also expressed FGF10 transcripts. During induction of the SV, FGF10 mRNA was present in m esenchyme surrounding the lower Wolffian ducts and, at later stages, FGF10 transcripts became restricted to mesenchymal cells subadjacent to the seros a. We investigated whether the FGF10 gene might be regulated by androgens b y analysing the levels of FGF10 transcripts in SV and VP organs grown in se rum-free organ culture. While FGF10 transcript levels increased after treat ment with testosterone in the SV (but not VP), these changes were not sensi tive to anti-androgen treatment, and thus it is likely that FGF10 mRNA was not directly regulated by testosterone. Also, FGF10 mRNA was observed in th e embryonic female reproductive tract in a position analogous to that of th e ventral prostate in males suggesting that FGF10 is not regulated by andro gens in vivo. Recombinant FGF10 protein specifically stimulated growth of D unning epithelial and BPH1 prostatic epithelial cell lines, but had no effe ct on growth of Dunning stromal cells or primary SV mesenchyme. Furthermore , FGF10 protein stimulated the development of ventral prostate and seminal vesicle organ rudiments in serum-free organ culture. When both FGF10 and te stosterone were added to organs in vitro, there was no synergistic inductio n of development, Additionally, development induced by FGF10 was not inhibi ted by the addition of the antiandrogen Cyproterone Acetate demonstrating t hat the effects of FGF10 were not mediated by the androgen receptor. Taken together, our experiments suggest that FGF10 functions as a mesenchymal par acrine regulator of epithelial growth in the prostate and seminal vesicle a nd that the FGF10 gene is not regulated by androgens,