Department of Clinical Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.
Stress. 2023 Nov;26(1):2247090. doi: 10.1080/10253890.2023.2247090.
As the end product of the hypothalamus-pituitary-adrenal (HPA) axis, the glucocorticoid hormones cortisol and corticosterone coordinate circadian activities, stress-coping, and adaptation to change. For this purpose, the hormone promotes energy metabolism and controls defense reactions in the body and brain. This life-sustaining action exerted by glucocorticoids occurs in concert with the autonomic nervous and immune systems, transmitters, growth factors/cytokines, and neuropeptides. The current contribution will focus on the glucocorticoid feedback paradox in the HPA-axis: the phenomenon that stress responsivity remains resilient if preceded by stress-induced secretion of glucocorticoid hormone, but not if this hormone is previously administered. Furthermore, in animal studies, the mixed progesterone/glucocorticoid antagonist RU486 or mifepristone switches to an apparent partial agonist upon repeated administration. To address these enigmas several interesting phenomena are highlighted. These include the conditional nature of the excitation/inhibition balance in feedback regulation, the role of glucose as a determinant of stress responsivity, and the potential of glucocorticoids in resetting the stress response system. The analysis of the feedback paradox provides also a golden opportunity to review the progress in understanding the role of glucocorticoid hormone in resilience and vulnerability during stress, the science that was burned deeply in Mary Dallman's emotions.
作为下丘脑-垂体-肾上腺 (HPA) 轴的终产物，糖皮质激素皮质醇和皮质酮协调昼夜活动、应对压力和适应变化。为此，激素促进能量代谢，并控制身体和大脑的防御反应。糖皮质激素发挥的这种维持生命的作用与自主神经系统和免疫系统、递质、生长因子/细胞因子和神经肽协同作用。本研究将重点介绍 HPA 轴中糖皮质激素反馈悖论：如果在应激诱导的糖皮质激素分泌之前发生应激反应，那么应激反应性仍然具有弹性，但如果先前给予这种激素，则不会发生这种情况。此外，在动物研究中，混合孕激素/糖皮质激素拮抗剂 RU486 或米非司酮在重复给药时会转变为明显的部分激动剂。为了解决这些谜团，强调了几个有趣的现象。这些现象包括反馈调节中兴奋/抑制平衡的条件性质、葡萄糖作为应激反应性决定因素的作用，以及糖皮质激素在重置应激反应系统中的潜力。对反馈悖论的分析也为回顾糖皮质激素在应激期间的弹性和脆弱性中的作用提供了一个绝佳的机会，这一科学深深地植根于玛丽·达尔曼的情感中。
