NF-κB and TNF-α stimulate androgen receptor expression in Sertoli cells
NF-κB and TNF-α stimulate androgen receptor expression in Sertoli cells
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DOI：
10.1016/s0303-7207(03)00005-4
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发表时间：
2003-03-28
影响因子：
4.1
通讯作者：
Walker, WH
中科院分区：
文献类型：
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作者：
Delfino, FJ;Boustead, JN;Walker, WH
哺乳动物睾丸内生殖细胞的发育需要睾酮通过与细胞内雄激素受体（AR）相互作用刺激体细胞支持细胞。AR表达水平在精子发生过程中发生显著变化，表明AR表达的调节是调节支持细胞对睾酮反应性的重要机制。AR基因启动子的分析揭示了与支持细胞p50和RelA NF-κ B蛋白相互作用的三个κ B增强子元件，并且这些NF-κ B亚基在支持细胞中的过表达刺激了AR启动子活性。此外，TNF-α，一种圆形精子细胞的分泌产物，刺激NF-κ B与AR启动子结合，诱导AR启动子活性，并增加支持细胞原代培养物中内源性AR表达。考虑到睾丸激素对精子发生的需求以及AR在介导支持细胞对睾丸激素的反应性中的重要性，NF-κ B和TNF-α刺激AR表达可能是维持有效精子发生所需的重要调节机制。(C)2003爱思唯尔科学爱尔兰有限公司保留所有权利。
Germ cell development within the mammalian testis requires testosterone stimulation of somatic Sertoli cells via interaction with intracellular androgen receptors (AR). AR expression levels undergo marked changes during spermatogenesis suggesting that the modulation of AR expression is an important mechanism to regulate Sertoli cell responsiveness to testosterone. An analysis of the AR gene promoter revealed three kappaB enhancer elements that interacted with Sertoli cell p50 and RelA NF-kappaB proteins, and the overexpression of these NF-kappaB subunits in Sertoli cells stimulated AR promoter activity. Moreover, TNF-alpha, a secretory product of round spermatids, stimulated NF-kappaB binding to the AR promoter, induced AR promoter activity, and increased endogenous AR expression in primary cultures of Sertoli cells. Given the requirement of testosterone for spermatogenesis and the importance of AR in mediating Sertoli cell responsiveness to testosterone, the stimulation of AR expression by NF-kappaB and TNF-alpha may represent an important regulatory mechanism required to maintain efficient spermatogenesis. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.