Leydig cells in the testes produce testosterone in the presence of gonadotropins. Therefore, male testosterone levels must oscillate within a healthy spectrum, given that elevated testosterone levels augment the risk of cardiovascular disorders. We observed that the expression of death-associated protein-like 1 (DAPL1), which is involved in the early stages of epithelial differentiation and apoptosis, is considerably higher in the testes of sexually mature mice than in other tissues. Accordingly, Dapl1-null mice were constructed to evaluate this variation. Notably, in these mice, the testicular levels of steroidogenic acute regulatory protein (StAR) and serum testosterone levels were significantly elevated on postnatal day 49. The findings were confirmed in vitro using I-10 mouse testis-derived tumor cells. The in vivo and in vitro data revealed the DAPL1-regulated the expression of StAR involving altered transcription of critical proteins in the protein kinase A and CREB/CREM pathways in Leydig cells. The collective findings implicate DAPL1 as an important factor for steroidogenesis regulation, and DAPL1 deregulation may be related to high endogenous levels of testosterone.

睾丸中的间质细胞在促性腺激素存在的情况下产生睾酮。因此，考虑到睾酮水平升高会增加心血管疾病的风险，男性睾酮水平必须在健康范围内波动。我们观察到，死亡相关蛋白样 1 (DAPL1) 参与上皮分化和细胞凋亡的早期阶段，在性成熟小鼠的睾丸中的表达显着高于其他组织。因此，构建Dapl1缺失小鼠来评估这种变异。值得注意的是，这些小鼠的睾丸生成类固醇急性调节蛋白 (StAR) 水平和血清睾酮水平在出生后第 49 天显着升高。使用 I-10 小鼠睾丸来源的肿瘤细胞在体外证实了这一发现。体内和体外数据显示，DAPL1 调节 StAR 的表达，涉及 Leydig 细胞中蛋白激酶 A 和 CREB/CREM 通路中关键蛋白转录的改变。集体发现表明 DAPL1 是类固醇生成调节的重要因素，并且 DAPL1 失调可能与高内源性睾酮水平有关。