Effects of prolonged ACTH-stimulation on adrenocortical cholesterol reserve and apolipoprotein e concentration in young and aged fischer 344 male rats
Effects of prolonged ACTH-stimulation on adrenocortical cholesterol reserve and apolipoprotein e concentration in young and aged fischer 344 male rats
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DOI：
10.1016/s0960-0760(98)00062-4
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发表时间：
1998-09-01
影响因子：
4.1
通讯作者：
Kowal, J
中科院分区：
文献类型：
--
作者：
Cheng, B;Chou, SC;Kowal, J
随着年龄的增长，大鼠肾上腺皮质的形态学变化包括脂滴和脂褐素颗粒的积累增加。由于腺体中胆固醇酯（CE）和载脂蛋白（apo）E的浓度也平行增加，因此衰老细胞中储存的胆固醇酯（CE）用于类固醇合成的脂滴利用或代谢可能会改变。为了探索这种可能性，在3-6月龄（mo）（Y）大鼠和20-23月龄（O）Fischer 344雄性大鼠中研究了肾上腺皮质胆固醇的储存和利用。两组大鼠每天接受促肾上腺皮质激素（ACTH 1 -39，Acthar凝胶）或单独使用明胶，连续7天。我们发现：（a）ACTH降低了O型大鼠的CE浓度，但Y型大鼠没有。刺激后5天内补充受刺激O大鼠中耗尽的CE。未能耗尽CE在刺激Y大鼠与激素的剂量不足，因为刺激Y动物与高剂量的ACTH实际上增加了CE浓度。与此相反，肾上腺皮质游离胆固醇浓度保持恒定的刺激过程中，无论年龄。(b)在刺激O大鼠耗尽的CE主要由肾上腺素胆固醇酯、花生四烯酸胆固醇酯和颈酸胆固醇酯组成。在刺激Y动物中累积的CE主要由胆固醇肾上腺酸酯、胆固醇花生四烯酸酯和胆固醇油酸酯组成。(c)而在刺激Y大鼠肾上腺apoE浓度下降，刺激O动物的浓度保持良好。(d)在体外，肾上腺匀浆或刺激O大鼠的胞浆组分显示出较高的能力，水解外源性CE比Y对应。然而，胆固醇酯化与外部脂肪酸底物肾上腺匀浆或微粒体馏分是可比的两个年龄组。我们的研究结果显示，改变肾上腺皮质胆固醇储备O大鼠，以科普长期ACTH刺激。apoE水平和CE水解活性的变化可能是与这种改变相关的因素。肾上腺皮质CE的消耗和积累反映在肾上腺素胆固醇和花生四烯酸胆固醇的平行变化，表明这些多不饱和脂肪酸在持续类固醇生成的生理重要性。(C)1998爱思唯尔科技有限公司。保留所有权利。
Changes in the morphology of rat adrenal cortex with age include increased accumulations of lipid droplets and lipofuscin granules. Because glandular concentrations of cholesteryl esters (CE) and apolipoprotein (apo) E are also increased in parallel, the utilization or metabolism of lipid-droplet stored CE for steroidogenesis might be altered in aging cells. To explore this possibility, adrenocortical cholesterol storage and utilization were studied in 3-6 months-old (mo) (Y) rats and 20-23 mo (O) Fischer 344 male rats. Both groups received either adrenocorticotropin (ACTH1-39, Acthar gel) or gelatin alone daily for seven consecutive days.We found that: (a) the CE concentration in O rats, but not Y animals, was diminished by ACTH. The depleted CE in stimulated-O rats was replenished within five days post stimulation. Failure to deplete CE in stimulated-Y rats was not associated with an insufficient dose of the hormone, since stimulation of Y animals with higher doses of ACTH actually increased the CE concentration. In contrast, adrenocortical free cholesterol concentration remained constant during stimulation regardless of age. (b) The depleted CE in stimulated-O rats was principally comprised of cholesteryl adrenate, cholesteryl arachidonate and cholesteryl cervonate. The accumulated CE in stimulated-Y animals was primarily comprised of cholesteryl adrenate, cholesteryl arachidonate and cholesteryl oleate. (c) Whereas in stimulated-Y rats adrenal apoE concentration declined, the concentration in stimulated O animals was well maintained. (d) In vitro, adrenal homogenate or cytosolic fraction from stimulated-O rats displayed a higher capacity to hydrolyze exogenous CE than its Y counterpart. However, cholesterol esterification with external fatty acid substrates in adrenal homogenate or microsomal fraction was comparable in the two age-groups.Our findings revealed altered adrenocortical cholesterol reserve in O rats to cope with prolonged ACTH-stimulation. Changes in apoE levels and CE hydrolysis activity may be factors associated with this alteration. Depletion and accumulation of adrenocortical CE are reflected in parallel changes in cholesteryl adrenate and cholesteryl arachidonate, suggesting physiologic importance of these polyunsaturated fatty acids during sustained steroidogenesis. (C) 1998 Elsevier Science Ltd. All rights reserved.