KERATINOCYTE GROWTH-FACTOR FUNCTIONS IN EPITHELIAL INDUCTION DURING SEMINAL-VESICLE DEVELOPMENT

Development of the seminal vesicle (SV) is elicited by androgens and i s dependent on epithelial-mesenchymal interactions. Androgenic signal transmission from the androgen-receptor-positive mesenchyme to the epi thelium has been postulated to involve paracrine factors. Keratinocyte growth factor (KGF), a member of the fibroblast growth factor family, is produced by stromal/mesenchymal cells and acts specifically on epi thelial cells. The KGF transcript was detected by reverse transcriptio n-polymerase chain reaction in newborn mouse SVs and by Northern blot analysis of RNA from cultured neonatal SV mesenchymal cells. Newborn S Vs placed in organ culture undergo androgen-dependent growth and diffe rentiation. Addition of a KGF-neutralizing monoclonal antibody to this system caused striking inhibition of both SV growth and branching mor phogenesis. This inhibition was due to a decline in epithelial prolife ration and differentiation, as the mesenchymal layer was not affected by anti-KGF treatment. When KGF (100 ng/ml) was substituted for testos terone in the culture medium, SV growth was almost-qual-to 50% that ob served with an optimal dose of testosterone (10(-7) M). All of these f indings suggest that KGF is present during a time of active SV morphog enesis and functions as an important mediator of androgen-dependent de velopment.