Ferrari Ettore, Magri Flavia
Department of Internal Medicine and Medical Therapy, University of Pavia, Via Alboino 21, 27100 Pavia, Italy.
Ageing Res Rev. 2008 Jul;7(3):225-33. doi: 10.1016/j.arr.2008.07.001. Epub 2008 Jul 10.
The pineal and pituitary-adrenocortical secretions play an important role in adaptive responses of the organism acting as coordinating signals for both several biological rhythms and multiple neuroendocrine and metabolic functions. The more relevant neuroendocrine changes occurring with ageing affect the secretion of melatonin and of corticosteroids. These changes may be clearly appreciated by the study of their circadian rhythmicity. The circadian profile of plasma melatonin was clearly flattened in elderly subjects and even more in old individuals with dementia. Indeed, the impairment of melatonin signal occurring in aging was related either to age itself or to the cognitive performances of subjects. The biosynthetic dissociation between glucocorticoids and androgen secretion is responsible for the selective impairment of androgens, such as DHEA and DHEA-S, by comparison to cortisol. Due to the opposite effects of the two kinds of corticosteroids either in the periphery and in the CNS, the imbalance between glucocorticoids and androgens, well demonstrated by the evaluation of the cortisol/DHEA-S molar ratio, may be responsible for the occurrence in the CNS of a more neurotoxic steroidal milieu, already present in clinically healthy elderly subjects and especially in patients with dementia. The effects of that steroidal milieu are more prominent at the level of the hippocampal-limbic structure, involved both in the modulation of endocrine structures, such as the HPA axis, and in the control of cognitive, behavioral and affective functions.
松果体及垂体 - 肾上腺皮质分泌物在机体的适应性反应中发挥重要作用，作为多种生物节律以及多种神经内分泌和代谢功能的协调信号。随着年龄增长发生的更为相关的神经内分泌变化会影响褪黑素和皮质类固醇的分泌。通过研究它们的昼夜节律性可以清楚地认识到这些变化。老年受试者血浆褪黑素的昼夜节律明显变平，在患有痴呆症的老年人中更为明显。实际上，衰老过程中发生的褪黑素信号受损与年龄本身或受试者的认知表现有关。与皮质醇相比，糖皮质激素和雄激素分泌之间的生物合成解离是雄激素（如脱氢表雄酮和硫酸脱氢表雄酮）选择性受损的原因。由于这两种皮质类固醇在周围和中枢神经系统中具有相反的作用，通过评估皮质醇/硫酸脱氢表雄酮摩尔比所证实的糖皮质激素和雄激素之间的失衡，可能是临床上健康的老年人尤其是痴呆症患者中枢神经系统中存在更具神经毒性的甾体环境的原因。这种甾体环境的影响在海马 - 边缘结构水平更为突出，该结构既参与调节内分泌结构（如HPA轴），也参与控制认知、行为和情感功能。
