Thomson A A, Foster B A, Cunha G R
Department of Anatomy, University of California, San Francisco, 94143-0452, USA.
Development. 1997 Jun;124(12):2431-9. doi: 10.1242/dev.124.12.2431.
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.
哺乳动物雄性附属生殖器官的发育需要雄激素以及间充质/上皮细胞间的相互作用。尽管这些旁分泌介质的具体身份尚不清楚，但有研究提出，表达受间充质和雄激素调控的旁分泌作用因子可调节这些器官的发育。角质形成细胞生长因子（Kgf）已被证明在小鼠精囊和大鼠腹侧前列腺的发育中起重要作用。此外，Kgf在间充质细胞中表达，并且在体外培养的前列腺细胞中已被证明受雄激素调控。因此，Kgf被认为是雄激素作用的一种介质。我们研究了大鼠精囊和前列腺发育过程中Kgf mRNA在体内和体外的表达情况。此外，我们还检测了Kgf受体（KgfR）、转化生长因子α（Tgfα）、表皮生长因子受体（EgfR）和细胞角蛋白19（CK19）的mRNA。在雄激素调控的发育过程中，生长因子和受体mRNA的水平有所波动；然而，这些变化反映的是间充质/上皮细胞比例的变化，而非睾酮的调控作用。Kgf的表达位于间充质，而KgfR位于上皮，Tgfα主要位于上皮。这些因子的mRNA水平变化与上皮标志物CK19水平的变化密切相关，表明它们是由于其表达所在组织区域相对丰度的改变所致。在精囊和前列腺的外植体培养中，Kgf已被证明可模拟雄激素的作用。我们在此证明，抗雄激素能够阻断Kgf刺激的发育，这表明Kgf和雄激素受体信号通路可能相互作用。综合我们的数据表明，在体内，Kgf可能与雄激素受体信号相互作用，但它不是雄激素作用的直接靶点。
