Azhar S, Reaven E
Geriatrics Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, Palo Alto, CA 94304, USA.
Mech Ageing Dev. 1994 Nov 25;77(1):13-25. doi: 10.1016/0047-6374(94)90043-4.
Previous studies from this laboratory have documented a progressive age-related decline in trophic hormone (or second messenger cAMP) stimulated corticosterone production in isolated adrenocortical cells. In the current study, we examined the possibility that the aging process exerts this effect by interfering with an early step in the delivery of lipoprotein-derived cholesteryl esters to the cell. As such, we monitored the ability of two different rat adrenocortical cell model systems (intact perfused adrenal glands and primary cultures of adrenocortical cells from 5- and 18- to 20-month-old rats) to internalize lipoprotein cholesteryl esters, and to convert the newly internalized cholesteryl esters to corticosterone production. The results indicate that lipoprotein (hHDL3 and rHDL) cholesteryl ester internalization (by both the endocytic and 'selective' pathways) is comparable in adrenocortical cells of the young and old rats. However, despite this, both the mass of corticosterone produced and the ratio of newly internalized (radiolabeled) cholesteryl ester incorporated into corticosterone is dramatically reduced in cells of the older animals. Thus, the lipoprotein uptake pathway appears to be intact in adrenals of older rats, but the intracellular processing of internalized cholesteryl ester is defective.
该实验室之前的研究记录了在分离的肾上腺皮质细胞中，与年龄相关的促营养激素（或第二信使环磷酸腺苷）刺激皮质酮生成的能力逐渐下降。在当前的研究中，我们探讨了衰老过程是否通过干扰脂蛋白衍生的胆固醇酯向细胞转运的早期步骤来发挥这种作用。因此，我们监测了两种不同的大鼠肾上腺皮质细胞模型系统（完整的灌注肾上腺以及来自5个月和18至20个月大的大鼠的肾上腺皮质细胞原代培养物）内化脂蛋白胆固醇酯以及将新内化的胆固醇酯转化为皮质酮生成的能力。结果表明，年轻和老年大鼠的肾上腺皮质细胞中脂蛋白（人高密度脂蛋白3和大鼠高密度脂蛋白）胆固醇酯的内化（通过内吞和“选择性”途径）相当。然而，尽管如此，老年动物细胞中产生的皮质酮量以及掺入皮质酮中的新内化（放射性标记）胆固醇酯的比例都显著降低。因此，老年大鼠肾上腺中脂蛋白摄取途径似乎是完整的，但内化胆固醇酯的细胞内加工存在缺陷。
