Kabler R L, Srinivasan A, Taylor L J, Mowad J, Rothblum L I, Cavanaugh A H
Department of Urology, Geisinger Clinic, Danville, PA 17822, USA.
J Steroid Biochem Mol Biol. 1996 Dec;59(5-6):431-9. doi: 10.1016/s0960-0760(96)00126-4.
Androgen-dependent growth of prostate tissue has been well documented. An additional prerequisite for cellular growth is the accumulation of ribosomes. It is thus reasonable to hypothesize that ribosomal DNA (rDNA) transcription in prostate tissue must be stimulated by androgen either directly or indirectly. This hypothesis was tested using both LNCaP cells, an androgen-dependent tissue culture line and in a rat animal model. Nuclear run-on assays confirmed that the administration of DHT to LNCaP cells resulted in a two- to three-fold increase in the rate of rRNA synthesis when compared to cells maintained in the absence of androgen. Enzymatic analysis and Western blots were carried out to measure the amount (activity and mass) of RNA polymerase I in DHT treated LNCaP cells. These assays demonstrated that neither the catalytic activity of RNA polymerase I nor the amount of the enzyme varied in response to DHT. However, Western blots revealed that the amount of the auxiliary RNA polymerase I transcription factor UBF, was significantly increased (two- to three-fold) in cells grown in the presence of DHT. Similar experiments were carried out with prostatic tissue obtained from orchiectomized rats maintained on either placebo or testosterone pellets. In this model, both the catalytic activity as well as the amount of RNA polymerase I protein decreased. However, in agreement with the tissue culture model, UBF protein decreased in prostates from orchiectomized rats and was maintained in animals supplemented with testosterone. These lines of evidence are consistent with the hypothesis that androgens stimulate rRNA synthesis by increasing the quantities of the components of the rDNA transcription system.
前列腺组织的雄激素依赖性生长已有充分记载。细胞生长的另一个先决条件是核糖体的积累。因此，合理推测前列腺组织中的核糖体DNA（rDNA）转录必定受到雄激素直接或间接的刺激。使用雄激素依赖性组织培养细胞系LNCaP细胞和大鼠动物模型对这一假设进行了验证。核转录分析证实，与未添加雄激素培养的细胞相比，向LNCaP细胞中添加双氢睾酮（DHT）会导致rRNA合成速率提高两到三倍。进行了酶分析和蛋白质免疫印迹，以测定经DHT处理的LNCaP细胞中RNA聚合酶I的量（活性和质量）。这些分析表明，RNA聚合酶I的催化活性和酶量均未因DHT而发生变化。然而，蛋白质免疫印迹显示，在添加DHT培养的细胞中，辅助RNA聚合酶I转录因子UBF的量显著增加（两到三倍）。对取自接受安慰剂或睾酮植入物的去势大鼠的前列腺组织进行了类似实验。在该模型中，RNA聚合酶I的催化活性和蛋白质含量均降低。然而，与组织培养模型一致，去势大鼠前列腺中的UBF蛋白减少，而在补充睾酮的动物中保持不变。这些证据支持了雄激素通过增加rDNA转录系统组分的量来刺激rRNA合成这一假设。
