de Kloet E R, Otte C, Kumsta R, Kok L, Hillegers M H J, Hasselmann H, Kliegel D, Joëls M
Division of Internal Medicine, Department of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.
Klinik für Psychiatrie und Psychotherapie, Charité Universitätsmedizin Campus Benjamin Franklin, Berlin, Germany.
J Neuroendocrinol. 2016 Aug;28(8). doi: 10.1111/jne.12379.
Cortisol and corticosterone act on the appraisal process, which comprises the selection of an appropriate coping style and the encoding of the experience for storage in the memory. This action exerted by the stress hormones is mediated by mineralocorticoid receptors (MRs), which are expressed abundantly in the limbic circuitry, particularly in the hippocampus. Limbic MR is down-regulated by chronic stress and during depression but induced by antidepressants. Increased MR activity inhibits hypothalamic-pituitary-adrenal axis activity, promotes slow wave sleep, reduces anxiety and switches circuit connectivity to support coping. Cortisol and emotion-cognition are affected by MR gene haplotypes based on rs5522 and rs2070951. Haplotype 1 (GA) moderates the effects of (early) life stressors, reproductive cycle and oral contraceptives. MR haplotype 2 (CA) is a gain of function variant that protects females against depression by association with an optimistic, resilient phenotype. Activation of MR therefore may offer a target for alleviating depression and cognitive dysfunction. Accordingly, the MR agonist fludrocortisone was found to enhance the efficacy of antidepressants and to improve memory and executive functions in young depressed patients. In conclusion, CORT coordinates via MR the networks underlying how an individual copes with stress, and this action is complemented by the widely distributed lower affinity glucocorticoid receptor (GR) involved in the subsequent management of stress adaptation. In this MR:GR regulation, the MR is an important target for promoting resilience.
皮质醇和皮质酮作用于评估过程，该过程包括选择合适的应对方式以及对经历进行编码以便存储在记忆中。应激激素的这种作用由盐皮质激素受体（MRs）介导，MRs在边缘系统回路中大量表达，尤其是在海马体中。边缘系统的MRs在慢性应激和抑郁期间下调，但可被抗抑郁药诱导。MRs活性增加会抑制下丘脑 - 垂体 - 肾上腺轴的活性，促进慢波睡眠，减轻焦虑并改变回路连接性以支持应对。基于rs5522和rs2070951的MR基因单倍型会影响皮质醇和情绪认知。单倍型1（GA）可调节（早期）生活应激源、生殖周期和口服避孕药的影响。MR单倍型2（CA）是一种功能获得性变体，通过与乐观、有复原力的表型相关联，保护女性免受抑郁困扰。因此，MRs的激活可能为缓解抑郁和认知功能障碍提供一个靶点。相应地，发现盐皮质激素受体激动剂氟氢可的松可增强抗抑郁药的疗效，并改善年轻抑郁症患者的记忆和执行功能。总之，皮质醇通过MRs协调个体应对压力的潜在网络，并且这种作用由广泛分布的低亲和力糖皮质激素受体（GR）在随后的应激适应管理中进行补充。在这种MRs：GR调节中，MRs是促进复原力的重要靶点。
