Age-related alterations of hypothalamic-pituitary-adrenal axis function in male Fischer 344 rats.
Age-related alterations of hypothalamic-pituitary-adrenal axis function in male Fischer 344 rats.
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DOI：
10.1210/endo.134.3.8119195
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发表时间：
1994-03
期刊：
影响因子：
4.8
通讯作者：
R. Hauger;K. Thrivikraman;P. Plotsky
中科院分区：
文献类型：
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作者：
R. Hauger;K. Thrivikraman;P. Plotsky
衰老通常与生理和认知过程的变化有关。在这些变化中，有一个明显的下丘脑-垂体-肾上腺轴的失调。在目前的实验中，比较了年轻(3-4月龄)和老年(21-24月龄)Fisher 344/N雄性大鼠下丘脑-垂体-肾上腺轴的功能。与年轻大鼠相比，老年大鼠在昼夜节律低谷期间基础ACTH和皮质酮水平升高。在昼夜节律的高峰期，青年和老年大鼠的血浆ACTH水平相当；然而，老年大鼠的皮质酮水平显著低于青年大鼠。刺激诱导的垂体-肾上腺激素的分泌在老年大鼠中被减弱。老年组对出血的ACTH反应仅为青年大鼠出血反应的45+/-3%。脑垂体对静脉注射CRF挑战的反应性是年轻人群的58+/-6%。这些变化与老年人群中垂体前叶CRF受体数量的38+/-5%的丢失有关。老年大鼠下丘脑对垂体-肾上腺功能的调节也有明显变化。老年大鼠(56+/-6 PM)下丘脑-门静脉血中CRF浓度显著高于青年大鼠(37+/-4 PM；P<；0.02，经双尾非配对t检验；n=8/组)，而门静脉精氨酸加压素水平在老年(0.56+/-0.01 nM)显著低于青年大鼠(0.89+/-0.01 nM；P<；0.01，经双尾非配对t检验；平均值+/-SEM；n=8/组)。老龄大鼠门脉CRF对出血的反应显著高于青年大鼠(P<；0.01)，而失血刺激的门静脉AVP水平升高则显著低于青年大鼠(P<；0.01)。最后，CRF含量的区域性分析显示，与青年大鼠相比，老年大鼠的正中隆起和额叶皮质显著减少，而原位杂交分析未能揭示与年龄相关的室旁CRF mRNA水平的差异。总体而言，这些观察结果与衰老与下丘脑CRF过度分泌和随后的促肾上腺皮质激素受体下调有关的假设是一致的。
Aging is frequently associated with changes in physiological and cognitive processes. Among these changes is a distinct dysregulation of the hypothalamic-pituitary-adrenal axis. In the current experiments, aspects of hypothalamic-pituitary-adrenal axis function were compared in young (3- to 4-month-old) and aged (21- to 24-month-old) Fisher 344/N male rats. Basal ACTH and corticosterone levels during the circadian trough were elevated in aged compared to young rats. During the evening peak of the circadian cycle, plasma ACTH levels in the young and aged rats were comparable; however, aged rats had significantly lower corticosterone levels than young rats. Stimulus-induced secretion of pituitary-adrenal hormones was attenuated in aged rats. The ACTH response to hemorrhage in the aged group was only 45 +/- 3% of the hemorrhage response in young rats. Pituitary responsiveness to an iv CRF challenge was 58 +/- 6% of that in the young population. These changes were associated with a 38 +/- 5% loss of anterior pituitary CRF receptor number in the aged population. Changes in the hypothalamic regulation of pituitary-adrenal function were also evident in the aged rats. Hypophysial-portal blood concentrations of CRF were significantly greater in aged (56 +/- 6 pM) compared to young rats (37 +/- 4 pM; P < 0.02, by two-tailed unpaired t test; n = 8/group), whereas portal levels of arginine vasopressin were significantly reduced in aged (0.56 +/- 0.01 nM) compared to young rats (0.89 +/- 0.01 nM; P < 0.01, by two-tailed unpaired t test; mean +/- SEM; n = 8/group). Portal CRF responses to hemorrhage were significantly (P < 0.01) greater in aged rats, whereas hemorrhage-stimulated increases in portal AVP levels were significantly (P < 0.01) reduced in the aged group compared to those in the young rats. Finally, regional assay of CRF content demonstrated significant reductions in the median eminence and frontal cortex of aged rats compared to young rats, whereas in situ hybridization analysis failed to reveal age-related differences in paraventricular CRF mRNA levels. Overall, these observations are consonant with the hypothesis that senescence is associated with hypothalamic CRF hypersecretion and a consequent down-regulation of corticotrope CRF receptor.