Transcriptional up-regulation of the human androgen receptor by androgen in bone cells.
Transcriptional up-regulation of the human androgen receptor by androgen in bone cells.
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DOI：
10.1210/endo.138.6.5163
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发表时间：
1997-06
期刊：
影响因子：
4.8
通讯作者：
K. Wiren;Xiao Wei Zhang;Chawnshang Chang;Edward J. Keenan;E. S. Orwoll
中科院分区：
文献类型：
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作者：
K. Wiren;Xiao Wei Zhang;Chawnshang Chang;Edward J. Keenan;E. S. Orwoll
在多种组织中观察到雄激素对雄激素受体（AR）表达的调节，通常表现为抑制作用，并被认为可减弱细胞对雄激素的反应。AR在成骨细胞（骨形成细胞）中表达，表明雄激素对骨的直接作用。在这里，我们的特点是雄激素暴露对人成骨细胞SaOS-2和U-2 OS细胞AR基因表达的影响。用非芳香化雄激素5 α-二氢睾酮处理成骨细胞以时间和剂量依赖性方式增加AR稳态信使RNA水平。在转染的培养物中，用与氯霉素乙酰转移酶基因连接的人AR启动子近端5 '侧翼区的2.3个酶进行的报告基因测定表明，雄激素对AR启动子活性的上调具有时间和剂量依赖性。用其他类固醇激素治疗，包括孕酮、17 β-雌二醇和地塞米松，没有效果。抗雄激素药羟氟沙星完全拮抗雄激素上调。因此，与许多其他雄激素靶组织相比，雄激素暴露增加成骨细胞中稳态AR信使RNA水平。这种调节至少部分发生在转录水平，由AR基因的5 '-启动子区介导，并且依赖于功能性AR。这些结果表明，生理浓度的雄激素对骨骼组织中的AR表达有显着影响。
Androgen regulation of androgen receptor (AR) expression has been observed in a variety of tissues, generally as inhibition, and is thought to attenuate cellular responses to androgen. AR is expressed in osteoblasts, the bone-forming cell, suggesting direct actions of androgens on bone. Here we characterized the effect of androgen exposure on AR gene expression in human osteoblastic SaOS-2 and U-2 OS cells. Treatment of osteoblastic cells with the nonaromatizable androgen 5alpha-dihydrotestosterone increased AR steady state messenger RNA levels in a time- and dose-dependent fashion. Reporter assays with 2.3 kilobases of the proximal 5'-flanking region of the human AR promoter linked to the chloramphenicol acetyltransferase gene in transfected cultures showed that up-regulation of AR promoter activity by androgen was time and dose dependent. Treatment with other steroid hormones, including progesterone, 17beta-estradiol, and dexamethasone, was without effect. The antiandrogen hydroxyflutamide completely antagonized androgen up-regulation. Thus, in contrast to many other androgen target tissues, androgen exposure increases steady state AR messenger RNA levels in osteoblasts. This regulation occurs at least partially at the level of transcription, is mediated by the 5'-promoter region of the AR gene, and is dependent on functional AR. These results suggest that physiological concentrations of androgens have significant effects on AR expression in skeletal tissue.