Scarpace P J
GRECC, VA Medical Center, Gainesville, FL 32602.
J Am Geriatr Soc. 1988 Nov;36(11):1067-71. doi: 10.1111/j.1532-5415.1988.tb04379.x.
In the three endocrine/neuroendocrine systems discussed, there are demonstrable declines in post-maturational responsiveness. Parathyroid hormone stimulation of 1,25-dihydroxyvitamin D production declines with age in the kidney as does calcium absorption in the intestine. Chronotropic and inotropic responsiveness to beta-adrenergic agonists decreases with age in the myocardium, and performance on passive avoidance tasks related to memory dysfunction declines with age in rodents. In each case there is a corresponding decrease in receptor activation with age. Parathyroid hormone receptors are less able to activate adenylate cyclase in older rat kidneys; beta-adrenergic receptors have reduced density in some tissues, demonstrate reduced agonist affinity (are uncoupled), and are less able to activate adenylate cyclase in most tissues with age; and muscarinic receptors demonstrate mixed agonist affinity (are uncoupled) with age in rat hippocampal cells. This reduction in receptor activation can be attributed to desensitization to increased agonist concentrations. Parathyroid hormone receptor activation is restored by parathyroidectomy, beta-adrenergic agonists no longer desensitize in older animals, and muscarinic receptors from senescent rats pharmacologically mimic desensitized receptors. However, desensitization of receptor activation cannot fully account for the reduced hormonal responsiveness in any of these systems. Parathyroidectomy does not restore 1,25-dihydroxyvitamin D production or intestinal calcium absorption. There are age-related post receptor deficits in beta-adrenergic pathway that are not mediated by changes in serum catecholamines. In conclusion, there are significant changes in receptor and post-receptor biochemistry with age. The overall decreases in hormonal responsiveness are not due to a single biochemical defect in the system and are probably multiple in nature.
在所讨论的三个内分泌/神经内分泌系统中，成熟后反应性出现了明显下降。随着年龄增长，甲状旁腺激素刺激肾脏产生1,25 - 二羟维生素D的能力下降，肠道对钙的吸收也随之下降。心肌对β - 肾上腺素能激动剂的变时性和变力性反应随年龄增长而降低，啮齿动物中与记忆功能障碍相关的被动回避任务表现也随年龄增长而下降。在每种情况下，受体激活都随年龄相应减少。老年大鼠肾脏中的甲状旁腺激素受体激活腺苷酸环化酶的能力降低；β - 肾上腺素能受体在某些组织中的密度降低，激动剂亲和力降低（解偶联），并且随着年龄增长，在大多数组织中激活腺苷酸环化酶的能力下降；毒蕈碱受体在大鼠海马细胞中随年龄表现出混合激动剂亲和力（解偶联）。受体激活的这种降低可归因于对激动剂浓度增加的脱敏。甲状旁腺切除术后甲状旁腺激素受体激活得以恢复，老年动物中β - 肾上腺素能激动剂不再脱敏，衰老大鼠的毒蕈碱受体在药理学上模拟脱敏受体。然而，受体激活的脱敏并不能完全解释这些系统中任何一个系统中激素反应性的降低。甲状旁腺切除术后并不能恢复1,25 - 二羟维生素D的产生或肠道对钙的吸收。β - 肾上腺素能途径中存在与年龄相关的受体后缺陷，这些缺陷不是由血清儿茶酚胺的变化介导的。总之，随着年龄增长，受体和受体后生物化学发生了显著变化。激素反应性的总体下降并非由于系统中的单一生化缺陷，可能本质上是多方面的。
