Augusto Taize M, Felisbino Sérgio L, Carvalho Hernandes F
Department of Cell Biology, State University of Campinas, CP6109, 13083-863 Campinas, SP, Brazil.
Cell Tissue Res. 2008 May;332(2):307-15. doi: 10.1007/s00441-008-0577-9. Epub 2008 Feb 16.
Androgen deprivation causes the rat ventral prostate to reduce to 10% of its original size by 21 days after castration. The regressive changes result from the loss of epithelial cells by apoptosis and marked reorganization of the stroma. We have investigated whether these changes are accompanied by variations in heparanase expression. The ventral prostate of castrated rats was collected and processed for the quantification of heparan sulfate (HS), for the measurement of heparanase expression and its localization by reverse transcription/polymerase chain reaction, Western blotting, and immunohistochemistry, and for transmission electron microscopy (TEM). Absolute HS content decreased significantly as early as day 7 after surgery. Heparanase mRNA peaked 7 days after castration. The heparanase proenzyme (65 kDa) and the active form (50 kDa) were identified and peaked on day 7 after castration; this coincided with maximum HS-degrading activity. Heparanase was located to the basolateral surface of epithelial cells and in the adjacent stroma. After castration, staining for heparanase was reduced in the epithelium and increased in the stroma. TEM revealed that the peak of heparanase expression at day 7 after castration was associated with extensive changes in the basement membrane of the epithelium, endothelium and smooth muscle cells involving cell shrinkage and/or deletion by apoptosis. These results suggest that heparanase expression increases after castration and correlates with a decreased amount of HS. This variation in heparanase expression is involved in tissue remodeling and in the control of the regressive pattern after 1 week of androgen deprivation.
去势后21天，雄激素剥夺使大鼠腹侧前列腺缩小至其原始大小的10%。这些退行性变化是由上皮细胞凋亡导致的丢失以及基质的显著重组引起的。我们研究了这些变化是否伴随着乙酰肝素酶表达的改变。收集去势大鼠的腹侧前列腺，进行硫酸乙酰肝素（HS）定量、通过逆转录/聚合酶链反应、蛋白质印迹法和免疫组织化学测定乙酰肝素酶表达及其定位，并进行透射电子显微镜（TEM）观察。术后第7天，绝对HS含量就显著下降。乙酰肝素酶mRNA在去势后7天达到峰值。鉴定出乙酰肝素酶原酶（65 kDa）和活性形式（50 kDa），并在去势后第7天达到峰值；这与最大的HS降解活性一致。乙酰肝素酶定位于上皮细胞的基底外侧表面和相邻的基质中。去势后，上皮细胞中乙酰肝素酶的染色减少，而基质中的染色增加。TEM显示，去势后第7天乙酰肝素酶表达的峰值与上皮、内皮和平滑肌细胞基底膜的广泛变化有关，这些变化涉及细胞凋亡导致的细胞收缩和/或缺失。这些结果表明，去势后乙酰肝素酶表达增加，且与HS量的减少相关。乙酰肝素酶表达的这种变化参与了组织重塑以及雄激素剥夺1周后退行性模式的控制。
