Abstract
Development of the mammalian male accessory sexual organs requires both androgens and mesenchymal/epithelial interactions. Paracrine acting factors whose expression is mesenchymal and androgen dependent have been proposed to regulate development of these organs, although the identity of these paracrine mediators is unknown. Keratinocyte growth factor (Kgf) has been shown to play an important role in the development of the mouse seminal vesicle and rat ventral prostate. Also, Kgf is expressed in mesenchymal cells and has been shown to be regulated by androgens 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), epidermal growth factor receptor (EgfR) and cytokeratin 19 (CK19). The levels of growth factor and receptor mRNAs fluctuated during androgen-regulated development; however, these changes reflected variations in the mesenchymal/epithelial ratio rather than regulation by testosterone. Expression of Kgf is mesenchymal, while KgfR is epithelial and Tgf alpha is predominantly epithelial. The changes in the levels of mRNAs for these factors correlated well with changes in the level of an epithelial marker, CK19, suggesting they were due to alterations in the relative abundance of tissue compartments in which they were expressed. Kgf has 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 suggest that, in vivo, Kgf may interact with androgen receptor signalling but it is not a direct target of androgen action.
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