Keratinocyte growth factor (KGF) can replace testosterone in the ductal branching morphogenesis of the rat ventral prostate

Int J Dev Biol. 1996 Oct;40(5):941-51.


Prostatic growth occurs through ductal elongation and branching into the mesenchyme. Ductal branching morphogenesis in the prostate is elicited by androgens via mesenchymal-epithelial interactions mediated by paracrine influences from mesenchyme. The role of keratinocyte growth factor (KGF) was investigated in the developing prostate as KGF has been suggested to be a paracrine acting factor. KGF transcripts were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in neonatal rat ventral prostates (VPs) in vivo, in VPs cultured in vitro, and in isolated VP mesenchyme. KGF receptor was detected in VP's by RT-PCR and was localized specifically to the epithelium by in situ hybridization. KGF was investigated as a potential paracrine mediator during androgen-induced prostatic development by examining neonatal rat VPs cultured for 6 days under serum-free conditions using a basal medium supplemented only with insulin and transferrin. When testosterone (10(-9) to 10(-8) M) was added to the basal medium, VPs grew and underwent ductal branching morphogenesis similar to that in situ. Neutralization of endogenous KGF with a monoclonal antibody to KGF (anti-KGF) or a soluble KGF receptor peptide inhibited androgen-stimulated VP growth (DNA content) and reduced the number of ductal end buds after 6 days of culture. When KGF (50 or 100 ng/ml) was added to the basal medium in the absence of testosterone, VP growth and ductal branching morphogenesis were stimulated. The number of ductal end buds was about 70% of that obtained with an optimal dose of testosterone (10(-8)M), and DNA content of VP's cultured with 100 ng/ml KGF was equivalent to that of glands cultured with testosterone. The stimulatory effect of KGF was partially blocked by cyproterone acetate, a steroidal anti-androgen. These data imply that KGF plays an important role as a mesenchymal paracrine mediator of androgen-induced epithelial growth and ductal branching morphogenesis in the rat VP.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • DNA / analysis
  • DNA / metabolism
  • Fibroblast Growth Factor 10
  • Fibroblast Growth Factor 7
  • Fibroblast Growth Factors*
  • Growth Substances / pharmacology*
  • Histocytochemistry
  • Image Processing, Computer-Assisted
  • In Situ Hybridization
  • Male
  • Mice
  • Morphogenesis / physiology*
  • Organ Culture Techniques
  • Polymerase Chain Reaction
  • Prostate / drug effects
  • Prostate / growth & development*
  • Prostate / metabolism
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Testosterone / pharmacology*
  • Transcription, Genetic / genetics


  • Antibodies, Monoclonal
  • Fgf7 protein, mouse
  • Fgf7 protein, rat
  • Fibroblast Growth Factor 10
  • Growth Substances
  • RNA, Messenger
  • Fibroblast Growth Factor 7
  • Testosterone
  • Fibroblast Growth Factors
  • DNA