Glibetic M, Larson D E, Rothblum L I, Sells B H
Department of Molecular Biology and Genetics, University of Guelph, Ontario, Canada.
Mol Cell Endocrinol. 1993 Aug;94(2):243-52. doi: 10.1016/0303-7207(93)90173-h.
The glucocorticoid analogue, dexamethasone, stimulated RNA synthesis more than two-fold in rat L6 myoblasts, without affecting the rate of cell proliferation. Treatment of myoblasts for 24 h with 10(-7) M dexamethasone resulted in a 30% increase in the cellular RNA level. More than a two-fold stimulation of pre-rRNA gene transcription by dexamethasone, as measured in isolated nuclei and by cell-free transcription, was accompanied by a corresponding increase in pre-rRNA levels. Co-incubation of myoblasts with cycloheximide and dexamethasone did not affect the enhanced pre-rRNA gene transcription demonstrating that de novo protein synthesis was unnecessary to manifest the dexamethasone effect on rDNA transcription. Support for this conclusion is provided by the finding that the levels of UBF1 and UBF2, rDNA upstream binding transcription factors, remain unchanged. The glucocorticoid antagonist RU38486 [11 beta-(4-dimethylaminophenyl)17 beta-hydroxy-17 alpha-(prop-1-ynyl)estra- 4,9-dien-3-one] inhibited the dexamethasone-stimulated rRNA gene transcription suggesting that the glucocorticoid receptor is involved in the response mechanism.
糖皮质激素类似物地塞米松可使大鼠L6成肌细胞中的RNA合成增加两倍以上,且不影响细胞增殖速率。用10⁻⁷M地塞米松处理成肌细胞24小时,可使细胞RNA水平提高30%。在分离的细胞核中以及通过无细胞转录测量发现,地塞米松对前体rRNA基因转录的刺激作用超过两倍,同时前体rRNA水平也相应增加。成肌细胞与环己酰亚胺和地塞米松共同孵育并不影响前体rRNA基因转录的增强,这表明从头合成蛋白质对于地塞米松对rDNA转录的作用并非必需。UBF1和UBF2(rDNA上游结合转录因子)水平保持不变这一发现为该结论提供了支持。糖皮质激素拮抗剂RU38486 [11β-(4-二甲基氨基苯基)17β-羟基-17α-(丙-1-炔基)雌-4,9-二烯-3-酮]抑制了地塞米松刺激的rRNA基因转录,提示糖皮质激素受体参与了该反应机制。