Vázquez D M
Mental Health Research Institute, University of Michigan, Ann Arbor 48109-0646, USA.
Psychoneuroendocrinology. 1998 Oct;23(7):663-700. doi: 10.1016/s0306-4530(98)00029-8.
The postnatal limbic-hypothalamic-pituitary-adrenal (LHPA) axis in the rodent is remarkably different from the adult, both in structure and function. The first 2 weeks postnatally are characterized by a 'silent period' during which the developing animal is hyporesponsive to stress (stress hyporesponsive period-SHRP), followed by a new and unique phase of stress responsiveness when the animal fails to swiftly terminate glucocorticoid secretion. In this review, we summarize our work which focuses on the regulatory biology of the components of the LHPA system and the consequences of its disruption on the adaptive responses of the developing organism. We find that the animal during the first 2 weeks of life responds to an intermittent chronic challenge increasing anterior pituitary POMC post-translational events, while the adult increases genomic events. The result for both the mature and the developing animal is the same, an increase in corticosterone (CS) levels. In addition, we have found evidence of impaired rate sensitive feedback in the weanling animal, as well as changes in ACTH clearance. Similar to the young animal emerging from SHRP, maternally deprived pups during the first week of life exhibit a substantial and sustained ACTH and CS response to stress. In the deprived animal these changes are accompanied by decreases in mineralocorticoid receptor gene expression in the hippocampus, suggesting that changes in mineralocorticoid to glucocorticoid receptor ratios may be important in this phenomena. What has become evident from our studies is that mechanisms underlying normal LHPA development are dynamic, age dependent and distinct to the strategies used by the mature organism to cope with stress.
啮齿动物出生后的边缘系统-下丘脑-垂体-肾上腺（LHPA）轴在结构和功能上与成年动物有显著差异。出生后的前两周以“沉默期”为特征，在此期间发育中的动物对应激反应低下（应激反应低下期-SHRP），随后是一个新的独特的应激反应阶段，此时动物无法迅速终止糖皮质激素分泌。在这篇综述中，我们总结了我们的工作，其重点是LHPA系统各组成部分的调节生物学及其破坏对发育中生物体适应性反应的影响。我们发现，出生后前两周的动物对间歇性慢性挑战的反应是增加垂体前叶POMC的翻译后事件，而成年动物则增加基因组事件。成熟动物和发育中动物的结果是相同的，即皮质酮（CS）水平升高。此外，我们发现了断奶动物中速率敏感反馈受损的证据，以及促肾上腺皮质激素清除率的变化。与从SHRP中出现的幼小动物类似，出生后第一周遭受母体剥夺的幼崽对应激表现出大量且持续的促肾上腺皮质激素和皮质酮反应。在被剥夺的动物中，这些变化伴随着海马中盐皮质激素受体基因表达的降低，这表明盐皮质激素与糖皮质激素受体比例的变化可能在这一现象中起重要作用。我们的研究中已经明确的是，正常LHPA发育的潜在机制是动态的、依赖年龄的，并且与成熟生物体应对应激所采用的策略不同。
