ANALYSIS OF GROWTH-FACTOR AND RECEPTOR MESSENGER-RNA LEVELS DURING DEVELOPMENT OF THE RAT SEMINAL-VESICLE AND PROSTATE

Development of the mammalian male accessory sexual organs requires bot h androgens and mesenchymal/epithelial interactions. Paracrine acting factors whose expression is mesenchymal and androgen dependent have be en proposed to regulate development of these organs, although the iden tity of these paracrine mediators is unknown. Keratinocyte growth fact or (Kgf) has been shown to play an important role in the development o f the mouse seminal vesicle and rat ventral prostate. Also, Kgf is exp ressed in mesenchymal cells and has been shown to be regulated by andr ogens in prostatic cells grown in vitro. Thus Kgf has been proposed as a mediator of androgen action. We have investigated the expression of Kgf mRNA during development of the rat seminal vesicle and prostate, both in vitro and in vivo. Additionally we have examined mRNAs for Kgf receptor (KgfR), transforming growth factor alpha (Tgf alpha), epider mal growth factor receptor (EgfR) and cytokeratin 19 (CK19). The level s of growth factor and receptor mRNAs fluctuated during androgen-regul ated development; however, these changes reflected variations in the m esenchymal/epithelial ratio rather than regulation by testosterone. Ex pression of Kgf is mesenchymal, while KgfR is epithelial and Tgf alpha is predominantly epithelial. The changes in the levels of mRNAs for t hese factors correlated well with changes in the level of an epithelia l marker, CK19, suggesting they were due to alterations in the relativ e abundance of tissue compartments in which they were expressed. Kgf h as been shown to mimic androgen action in explant cultures of seminal vesicle and prostate. We demonstrate here that anti-androgens are able to block Kgf stimulated development, suggesting that Kgf and androgen receptor signalling pathways may interact. Taken together our data su ggest that, in vivo, Kgf may interact with androgen receptor signallin g but it is not a direct target of androgen action.