Thorngate Fayanne E, Strockbine Penelope A, Erickson Sandra K, Williams David L
Department of Pharmacological Sciences, University Medical Center, State University of New York at Stony Brook, Stony Brook, NY 11794, USA.
J Lipid Res. 2002 Nov;43(11):1920-6. doi: 10.1194/jlr.m200205-jlr200.
Previous studies suggest the hypothesis that apoE produced by adrenocortical cells modulates cellular cholesterol metabolism to enhance the storage of esterified cholesterol (EC) at the expense of cholesterol delivery to the steroidogenic pathway. In the present study, parameters of adrenal cholesterol metabolism and corticosteroid production were examined in wild type and apoE-deficient (apoe(-/-)) mice. Adrenal gland EC content and the EC/free cholesterol (FC) ratio in mice stressed by adrenocorticotropin (ACTH) treatment or saline injection were reduced in apoe(-/-) compared to apoe(+/+) mice. Relative to apoe(+/+) mice, apoE deficiency also resulted in increased levels of plasma corticosterone in the basal state, in response to acute or long-term ACTH treatment, and after a swim-induced neuroendocrine-directed stress test. Measurements of adrenal gland scavenger receptor class B, type I (SR-BI), LDL receptor, and LDL receptor related protein (LRP) levels and the activities of ACAT or HMG-CoA reductase showed no difference between genotypes. Apoe(-/-) and apoe(+/+) mice showed similar quantitative increases in LDL receptors, SR-BI, adrenal weight gain, and ACAT activities in response to ACTH, and both genotypes had similar basal plasma ACTH concentrations. These results suggest that the effects of apoE deficiency reflect events at the level of the adrenal gland and are specific to changes in cholesterol accumulation and corticosterone production. Further, these findings support the hypothesis that apoE acts to enhance adrenocortical EC accumulation and diminish corticosterone production.
先前的研究提出了一个假说，即肾上腺皮质细胞产生的载脂蛋白E（apoE）调节细胞胆固醇代谢，以增加酯化胆固醇（EC）的储存，代价是减少胆固醇向类固醇生成途径的输送。在本研究中，我们检测了野生型和apoE基因缺陷（apoe(-/-)）小鼠的肾上腺胆固醇代谢参数和皮质类固醇生成情况。与apoE基因野生型（apoe(+/+)）小鼠相比，经促肾上腺皮质激素（ACTH）处理或注射生理盐水应激的apoe(-/-)小鼠的肾上腺EC含量以及EC/游离胆固醇（FC）比值降低。相对于apoe(+/+)小鼠，apoE缺乏还导致基础状态下、急性或长期ACTH处理后以及游泳诱导的神经内分泌应激试验后血浆皮质酮水平升高。肾上腺I型清道夫受体B类（SR-BI）、低密度脂蛋白受体（LDL受体）和低密度脂蛋白受体相关蛋白（LRP）水平的测量以及酰基辅酶A胆固醇酰基转移酶（ACAT）或3-羟基-3-甲基戊二酰辅酶A还原酶（HMG-CoA还原酶）的活性在不同基因型之间没有差异。apoe(-/-)和apoe(+/+)小鼠对ACTH的反应在LDL受体、SR-BI、肾上腺重量增加和ACAT活性方面表现出相似的定量增加，并且两种基因型的基础血浆ACTH浓度相似。这些结果表明，apoE缺乏的影响反映了肾上腺水平的事件，并且特定于胆固醇积累和皮质酮生成的变化。此外，这些发现支持了apoE起到增强肾上腺皮质EC积累并减少皮质酮生成的假说。
