Roth G S
Biochim Biophys Acta. 1975 Jul 14;399(1):145-56. doi: 10.1016/0304-4165(75)90221-4.
Glucocorticoids are 63% less effective in inhibiting [5-3-h] uridine uptake by splenic leukocytes of senescent rats (24-14 months) than by those of mature adult animals (12-14 months). Scatchard analyses reveal 57% fewer specific glucocorticoid binding sites in cytosols of the senescent group. Reduced binding of cortisol by cytosol macromolecules of intact viable leukocytes at 37 degrees C is also apparent in the older rats. Specific binding of glucocorticoids to cytoplasmic macromolecules appears to be closely linked, if not required, for inhibition of [5-3-hi1 uridine uptake. This is evidenced by the fact that both inhibition and specific binding are simultaneously blocked by progesterone administration. In addition, the amount of specific binding as well as the degree of inhibition of [5-3-h] uridine uptake is concentration dependent up to 2. 10-6 M cortisol. Thus, decreased glucocorticoid reponsiveness in the cells from senescent rats appears to be due primarily to decreased concentrations of specific glucocorticoid receptors.
糖皮质激素对老年大鼠(24 - 14个月)脾脏白细胞摄取[5 - 3 - h]尿苷的抑制作用比对成年成熟动物(12 - 14个月)的抑制作用低63%。斯卡查德分析显示,老年组细胞溶质中的特异性糖皮质激素结合位点比成年组少57%。在37摄氏度时,老年大鼠完整存活白细胞的细胞溶质大分子对皮质醇的结合减少也很明显。糖皮质激素与细胞质大分子的特异性结合似乎与抑制[5 - 3 - h]尿苷摄取密切相关,即便不是必需的。这一点可由以下事实证明:给予孕酮会同时阻断抑制作用和特异性结合。此外,特异性结合量以及对[5 - 3 - h]尿苷摄取的抑制程度在皮质醇浓度高达2×10⁻⁶ M时呈浓度依赖性。因此,老年大鼠细胞中糖皮质激素反应性降低似乎主要是由于特异性糖皮质激素受体浓度降低所致。