Quarmby V E, Yarbrough W G, Lubahn D B, French F S, Wilson E M
Laboratories for Reproductive Biology, University of North Carolina, Chapel Hill 27599.
Mol Endocrinol. 1990 Jan;4(1):22-8. doi: 10.1210/mend-4-1-22.
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.
使用以雄激素受体（AR）cDNA片段为探针的Northern印迹分析来研究AR mRNA的自身调节。在大鼠腹侧前列腺、凝固腺、附睾、精囊、肾脏和大脑以及人前列腺癌细胞系LNCaP中，雄激素撤除后AR mRNA的量增加2至10倍，而雄激素刺激后则降至对照水平以下。在大鼠腹侧前列腺中，去势后24小时内AR mRNA增加2至3倍，并在4天内保持升高。去势后24小时开始用丙酸睾酮治疗，在雄激素替代的8小时内腹侧前列腺AR mRNA降低4倍。去势后24小时给予雌二醇对前列腺AR mRNA无显著影响。包括睾酮和合成雄激素甲基三烯olone（R1881）在内的雄激素，或抗雄激素醋酸环丙孕酮在体外对LNCaP细胞中的AR mRNA有下调作用，而雌二醇则无作用。给雄激素不敏感的大鼠注射丙酸睾酮不会降低AR mRNA。因此，雄激素对AR mRNA的下调是一个受体介导的过程，发生在体内雄激素反应性不同的大鼠组织以及培养的人前列腺细胞中。
