AUTOLOGOUS DOWN-REGULATION OF ANDROGEN RECEPTOR MESSENGER-RIBONUCLEIC-ACID
AUTOLOGOUS DOWN-REGULATION OF ANDROGEN RECEPTOR MESSENGER-RIBONUCLEIC-ACID
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DOI：
10.1210/mend-4-1-22
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发表时间：
1990-01-01
影响因子：
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通讯作者：
WILSON, EM
中科院分区：
文献类型：
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作者：
QUARMBY, VE;YARBROUGH, WG;WILSON, EM
以雄激素受体（AR）cDNA片段为探针，采用北方印迹分析研究了AR mRNA的自动调节。AR mRNA的量增加2- 10倍，雄激素戒断和雄激素刺激后，大鼠腹侧前列腺，前列腺，附睾，精囊，肾脏和大脑，并在人类前列腺癌细胞系，LNCaP的控制水平以下下降。在大鼠腹侧前列腺，AR mRNA增加2至3倍，在24小时内去势后，并保持4天的升高。去势后24小时开始用丙酸睾酮治疗，在雄激素替代后8小时内使腹侧前列腺AR mRNA降低4倍。去势后24 h给予雌二醇对前列腺AR mRNA无明显影响。雄激素，包括睾酮和合成雄激素methyltrienolone（R1881），或抗雄激素醋酸环丙孕酮下调AR mRNA在体外LNCaP细胞，而雌二醇没有影响。给雄激素不敏感的大鼠施用丙酸睾酮并不降低AR mRNA。因此，雄激素对AR mRNA的下调是一种受体介导的过程，其发生在雄激素反应性不同的大鼠组织和培养的人前列腺细胞中。
Autoregulation of androgen receptor (AR) mRNA was investigated using Northern blot analysis with AR cDNA fragments as probes. The amount of AR mRNA increased 2- to 10-fold with androgen withdrawal and decreased below control levels after androgen stimulation in rat ventral prostate, coagulating gland, epididymis, seminal vesicle, kidney, and brain, and in a human prostate cancer cell line, LNCaP. In rat ventral prostate, AR mRNA increased 2- to 3-fold within 24 h after castration and remained elevated for 4 days. Treatment with testosterone propionate beginning 24 h after castration reduced ventral prostate AR mRNA 4-fold within 8 h of androgen replacement. Administration of estradiol 24 h after castration had no significant effect on prostatic AR mRNA. Androgens, including testosterone and the synthetic androgen methyltrienolone (R1881), or the antiandrogen cyproterone acetate down-regulated AR mRNA in vitro in LNCaP cells, whereas estradiol was without effect. Administration of testosterone propionate to rats with androgen insensitivity did not decrease AR mRNA. Down-regulation of AR mRNA by androgen is therefore a receptor-mediated process which occurs in vivo in rat tissues that differ in androgen responsiveness and in cultured human prostate cells.