Sugimura Y, Cunha G R, Bigsby R M
Prostate. 1986;9(3):217-25. doi: 10.1002/pros.2990090302.
It has been shown previously that wild-type urogenital sinus mesenchyme can induce the formation of prostate-like glandular structures in urinary bladder epithelium derived from adult Tfm (testicular feminization) mice. Total DNA synthesis within these tissue recombinants has been shown biochemically to be androgen sensitive. To determine which tissue (epithelium or stroma) accounts for this androgen-dependent DNA synthesis, an autoradiographic study was performed with tissue recombinants composed of rat wild-type urogenital sinus mesenchyme (UGM) associated with bladder epithelium from either wild-type (BLE) or Tfm mice (Tfm BLE). Both types of recombinants were grown under the kidney capsule of male athymic nude mice for 4 weeks. The hosts were then castrated, and 2 weeks later were treated with either testosterone propionate (TP), TP plus cyproterone acetate (CA), or oil vehicle for 3 days. DNA synthetic activity was measured through analysis of labelling index (LI) after incorporation of 3[H]-thymidine in vivo. For both UGM + BLE and UGM + Tfm BLE recombinants thymidine incorporation in epithelial cells greatly exceeded that of the stromal cells. TP stimulated epithelial LI to a similar degree (about 50- to 200-fold greater than controls) in both UGM + BLE and UGM + Tfm BLE recombinants; CA antagonized the effect of TP. Nuclear 3H-DHT binding was observed autoradiographically within the epithelial cells of the induced epithelium of UGM + wild-type BLE recombinants, but not within epithelium of UGM + Tfm BLE recombinants. Wild-type mesenchymal cells in both tissue recombinants showed specific nuclear 3H-DHT uptake. Thus, the proliferative effect of androgens upon prostatic epithelium is not a direct effect mediated by intra-epithelial androgen receptors, but rather it appears to be elicited indirectly via regulatory influences from androgen-receptor-positive stromal cells.
先前的研究表明，野生型泌尿生殖窦间充质能够诱导成年睾丸雌性化（Tfm）小鼠来源的膀胱上皮中前列腺样腺结构的形成。这些组织重组体中的总DNA合成在生化上已显示对雄激素敏感。为了确定哪种组织（上皮或基质）导致了这种雄激素依赖性DNA合成，对由大鼠野生型泌尿生殖窦间充质（UGM）与野生型（BLE）或Tfm小鼠（Tfm BLE）的膀胱上皮组成的组织重组体进行了放射自显影研究。两种类型的重组体在雄性无胸腺裸鼠的肾包膜下培养4周。然后对宿主进行阉割，2周后用丙酸睾酮（TP）、TP加醋酸环丙孕酮（CA）或油性载体处理3天。通过分析体内掺入3[H]-胸腺嘧啶后的标记指数（LI）来测量DNA合成活性。对于UGM + BLE和UGM + Tfm BLE重组体，上皮细胞中的胸腺嘧啶掺入量大大超过基质细胞。TP在UGM + BLE和UGM + Tfm BLE重组体中均以相似程度刺激上皮LI（比对照高约50至200倍）；CA拮抗TP的作用。在UGM +野生型BLE重组体诱导上皮的上皮细胞内通过放射自显影观察到核3H-DHT结合，但在UGM + Tfm BLE重组体的上皮内未观察到。两种组织重组体中的野生型间充质细胞均显示出特异性的核3H-DHT摄取。因此，雄激素对前列腺上皮的增殖作用不是由上皮内雄激素受体介导的直接作用，而是似乎通过雄激素受体阳性基质细胞的调节影响间接引发的。
