Prescott J L, Tindall D J
Department of Biochemistry and Molecular Biology, Mayo Foundation, Rochester, Minnesota 55905, USA.
Endocrinology. 1998 Apr;139(4):2111-9. doi: 10.1210/endo.139.4.5926.
Androgens are required for the development and function of the prostate. In a normal human prostate, androgens control the synthesis of proteins such as prostate-specific antigen and human glandular kallikrein. The prostate secretes these proteins as well as a number of other compounds to form the prostatic fluid. Using differential display PCR to detect novel androgen-regulated genes, clathrin heavy chain expression was identified as potentially being up-regulated by androgens in the prostate cancer cell line LNCaP. We report here that the clathrin heavy chain and light chain genes are regulated by androgens. Clathrin heavy chain messenger RNA was up-regulated by androgens in a concentration- and time-specific manner in the LNCaP cell line. Translation of clathrin heavy chain messenger RNA was stimulated by androgens. Steady state levels of clathrin light chains a and b were up-regulated in the presence of androgen in LNCaP cells. Clathrin gene expression was examined in normal rat prostates, and similar results were found. Clathrin heavy chain protein levels in the rat prostate are also affected by the androgen status of the animal. We hypothesize that clathrin may be involved in the exocytosis of androgen-regulated secretory proteins such as prostate-specific antigen and human glandular kallikrein.
雄激素对于前列腺的发育和功能至关重要。在正常人类前列腺中,雄激素控制前列腺特异性抗原和人腺体激肽释放酶等蛋白质的合成。前列腺分泌这些蛋白质以及许多其他化合物以形成前列腺液。利用差异显示PCR检测新的雄激素调节基因,发现网格蛋白重链表达在前列腺癌细胞系LNCaP中可能被雄激素上调。我们在此报告,网格蛋白重链和轻链基因受雄激素调节。在LNCaP细胞系中,雄激素以浓度和时间特异性方式上调网格蛋白重链信使RNA。雄激素刺激网格蛋白重链信使RNA的翻译。在LNCaP细胞中,雄激素存在时网格蛋白轻链a和b的稳态水平上调。在正常大鼠前列腺中检测了网格蛋白基因表达,发现了类似结果。大鼠前列腺中网格蛋白重链蛋白水平也受动物雄激素状态的影响。我们推测,网格蛋白可能参与雄激素调节的分泌蛋白如前列腺特异性抗原和人腺体激肽释放酶的胞吐作用。