Delfino Frank J, Boustead Jared N, Fix Charity, Walker William H
Department of Cell Biology and Physiology, University of Pittsburgh, 820 Scaife Hall, 3550 Terrace Street, PA 15261, USA.
Mol Cell Endocrinol. 2003 Mar 28;201(1-2):1-12. doi: 10.1016/s0303-7207(03)00005-4.
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.
哺乳动物睾丸内的生殖细胞发育需要睾酮通过与细胞内雄激素受体（AR）相互作用来刺激体细胞支持细胞。在精子发生过程中，AR表达水平会发生显著变化，这表明AR表达的调节是调控支持细胞对睾酮反应性的重要机制。对AR基因启动子的分析揭示了三个κB增强子元件，它们与支持细胞的p50和RelA NF-κB蛋白相互作用，并且这些NF-κB亚基在支持细胞中的过表达刺激了AR启动子活性。此外，圆形精子细胞的分泌产物肿瘤坏死因子-α（TNF-α）刺激NF-κB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的内源性AR表达。鉴于睾酮对精子发生的必要性以及AR在介导支持细胞对睾酮反应性中的重要性，NF-κB和TNF-α对AR表达的刺激可能代表了维持高效精子发生所需的重要调节机制。
