Scaccianoce S, Nicolai R, Cigliana G, Angelucci L
Institute of Pharmacology, Medical Faculty, University, La Sapienza, Rome, Italy.
Neuroendocrinology. 1995 Jul;62(1):32-8. doi: 10.1159/000126985.
Aging, as well as some frequently associated pathological conditions (depression, dementia, Alzheimer's disease, etc.), has been shown to have a profound impact on the normal functioning of the hippocampus-hypothalamo-pituitary-adrenocortical axis system. The hypothalamo-pituitary-adrenocortical axis in the aged rat is characterized by an increase in the basal level of circulating corticosterone, an impaired ability to recover from the adrenocortical stress response, and a reduced sensitivity to the dexamethasone suppression test. All these alterations may arise from a reduced hippocampal negative feedback control of the axis, as suggested by the age-dependent loss of hippocampal adrenocorticoid receptors. Among the hypothalamic corticotropin secretagogues, corticotropin-releasing hormone (CRH) and arginine-vasopressin (AVP) are considered the main physiological mediators of hypothalamic control of ACTH release. Thus, we have investigated the dynamic and the temporal course of the adrenocortical response to CRH and AVP in the aged rat. Freely moving jugular-catheterized male Sprague-Dawley rats (3- and 24-month-old) were injected with CRH (0.5, 0.05 and 0.01 microgram/kg i.v.), or AVP (1.0, 0.1 and 0.05 microgram/kg i.v.), or CRH and AVP in combination. In addition, adrenocortical sensitivity to corticotropin has been studied by injecting ACTH (10 ng/kg i.v.). Our study has (1) indicated that the response to ACTH secretagogues is dampened with aging, and (2) shown in the aged rat a slower recovery. Moreover, the results had confirmed the age-dependent increase in the basal level of corticosterone in the rat, and shown no age-related differences in the glucocorticoid response to ACTH.
衰老以及一些常见的相关病理状况（如抑郁症、痴呆症、阿尔茨海默病等）已被证明对海马体 - 下丘脑 - 垂体 - 肾上腺皮质轴系统的正常功能有深远影响。老年大鼠的下丘脑 - 垂体 - 肾上腺皮质轴的特征是循环皮质酮的基础水平升高、从肾上腺皮质应激反应中恢复的能力受损以及对地塞米松抑制试验的敏感性降低。所有这些改变可能源于海马体对该轴的负反馈控制减弱，这一点由海马体促肾上腺皮质激素受体随年龄增长而丧失所表明。在下丘脑促肾上腺皮质激素释放因子中，促肾上腺皮质激素释放激素（CRH）和精氨酸加压素（AVP）被认为是下丘脑控制促肾上腺皮质激素释放的主要生理介质。因此，我们研究了老年大鼠肾上腺皮质对CRH和AVP反应的动态变化和时间进程。对自由活动的、经颈静脉插管的雄性斯普拉格 - 道利大鼠（3个月和24个月大）静脉注射CRH（0.5、0.05和0.01微克/千克）、AVP（1.0、0.1和0.05微克/千克）或CRH与AVP的组合。此外，通过静脉注射促肾上腺皮质激素（10纳克/千克）研究了肾上腺皮质对促肾上腺皮质激素的敏感性。我们的研究（1）表明，随着年龄增长，对促肾上腺皮质激素释放因子的反应减弱，（2）显示老年大鼠恢复较慢。此外，结果证实了大鼠皮质酮基础水平随年龄增长而升高，并且显示出对促肾上腺皮质激素的糖皮质激素反应无年龄相关差异。
