title: Keratinocyte growth factor (KGF) can replace testosterone in the ductal branching morphogenesis of the rat ventral prostate.
abstract: 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.
authors.affiliation: Department of Urology, Aichi Cancer Center, Nagoya, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sugimura
authors.forename: B A
authors.initials: BA
authors.lastname: Foster
authors.forename: Y K
authors.initials: YK
authors.lastname: Hom
authors.forename: J H
authors.initials: JH
authors.lastname: Lipschutz
authors.forename: J S
authors.initials: JS
authors.lastname: Rubin
authors.forename: P W
authors.initials: PW
authors.lastname: Finch
authors.forename: S A
authors.initials: SA
authors.lastname: Aaronson
authors.forename: N
authors.initials: N
authors.lastname: Hayashi
authors.forename: J
authors.initials: J
authors.lastname: Kawamura
authors.forename: G R
authors.initials: GR
authors.lastname: Cunha
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D004247:DNA / Q000032:analysis / Q000378:metabolism; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D006133:Growth Substances / Q000494:pharmacology*; D006651:Histocytochemistry; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D009024:Morphogenesis / Q000502:physiology*; D009924:Organ Culture Techniques; D016133:Polymerase Chain Reaction; D011467:Prostate / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; C496454:Fgf7 protein, mouse; C496455:Fgf7 protein, rat; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D012333:RNA, Messenger; D051523:Fibroblast Growth Factor 7; D013739:Testosterone; D005346:Fibroblast Growth Factors; D004247:DNA