Glial cell line-derived neurotrophic factor (GDNF) and retinoic acid (RA) are two molecules crucial for the regulation of the spermatogonial compartment of the testis. During the cycle of the seminiferous epithelium, their relative concentration oscillates with lower GDNF levels in stages where RA levels are high. It has been recently shown that RA negatively regulates Gdnf expression but the mechanisms behind are so far unknown. Here, we show that RA directly downregulates Gdnf mRNA levels in primary murine Sertoli cells through binding of RARα to a novel DR5-RARE on Gdnf promoter. Pharmacological inhibition and chromatin immunoprecipitation-quantitative polymerase chain reaction analysis suggested that the underlying mechanism involved histone deacetylase activity and epigenetic repression of Gdnf promoter upon RA treatment.

中文翻译：

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维甲酸在Sertoli细胞中对Gdnf表达的调节。

胶质细胞源性神经营养因子（GDNF）和视黄酸（RA）是调节睾丸精原区室至关重要的两个分子。在生精上皮的周期中，它们的相对浓度在RA水平高的阶段以较低的GDNF水平振荡。最近显示，RA负调节Gdnf的表达，但目前尚不清楚其背后的机制。在这里，我们显示RA通过将RARα结合到Gdnf启动子上的新型DR5-RARE上，直接下调原代小鼠支持细胞中Gdnf mRNA的水平。药理抑制和染色质免疫沉淀-定量聚合酶链反应分析表明，其潜在的机制涉及组蛋白脱乙酰基酶活性和RA处理后Gdnf启动子的表观遗传抑制。