Division of BioTherapeutics, Leiden Academic Centre for Drug Research, 2333CC, Leiden, the Netherlands.
Division of BioTherapeutics, Leiden Academic Centre for Drug Research, 2333CC, Leiden, the Netherlands.
Mol Cell Endocrinol. 2019 Jun 15;490:21-27. doi: 10.1016/j.mce.2019.04.001. Epub 2019 Apr 3.
Apolipoprotein E (APOE) deficient mice exhibit unexplained hypercorticosteronemia. Given that APOE is also produced locally within the adrenals, we evaluated the effect of adrenal-specific APOE deficiency on the glucocorticoid function. Hereto, one adrenal containing or lacking APOE was transplanted into adrenalectomized wild-type mice. Adrenal APOE deficiency did not impact adrenal total cholesterol levels. Importantly, the ability of the two adrenal types to produce glucocorticoids was also not different as judged from the similar plasma corticosterone levels. Adrenal mRNA expression levels of HMG-CoA reductase and the LDL receptor were decreased by respectively 72% (p < 0.01) and 65% (p = 0.07), suggesting that cholesterol acquisition pathways were inhibited to possibly compensate the lack of APOE. In support, a parallel increase in the expression level of the cholesterol accumulation-associated ER stress marker CHOP was detected (+117%; p < 0.05). In conclusion, our studies show that elimination of adrenocortical APOE production does not impact glucocorticoid output in wild-type mice.
载脂蛋白 E（APOE）缺陷小鼠表现出无法解释的皮质醇增多症。鉴于 APOE 也在肾上腺内局部产生，我们评估了肾上腺特异性 APOE 缺乏对糖皮质激素功能的影响。为此，将含有或缺乏 APOE 的一个肾上腺移植到肾上腺切除的野生型小鼠中。肾上腺 APOE 缺乏不影响肾上腺总胆固醇水平。重要的是，从类似的血浆皮质酮水平判断，两种肾上腺类型产生糖皮质激素的能力也没有差异。HMG-CoA 还原酶和 LDL 受体的肾上腺 mRNA 表达水平分别降低了 72%（p < 0.01）和 65%（p = 0.07），表明胆固醇摄取途径受到抑制，可能是为了补偿 APOE 的缺乏。支持这一观点的是，检测到与胆固醇积累相关的 ER 应激标志物 CHOP 的表达水平平行增加（+117%；p < 0.05）。总之，我们的研究表明，在野生型小鼠中消除肾上腺皮质 APOE 的产生并不影响糖皮质激素的输出。
