DeRijk Roel, de Kloet E Ronald
Department of Psychiatry, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands.
Endocrine. 2005 Dec;28(3):263-70. doi: 10.1385/ENDO:28:3:263.
A fundamental question in the neuroendocrinology of stress-related psychopathology is why some individuals flourish and others perish under similar adverse conditions. In this contribution we focus on the variants of mineralocorticorticoid (MR) and glucocorticoid receptors (GR) that operate in balance and coordinate behavioral, autonomic, and neuroendocrine response patterns involved in homeostasis and health. In the GR-gene, three single nucleotide polymorphism (SNPs) have been associated with changes in metabolic profile and cardiovascular parameters: the ER22/23EK with a favorable and the N363S and the Bcl1 with a more adverse profile. Importantly, the N363S and the Bcl1 are found to increase cortisol responses to a psychosocial stressor. As a result, the whole body will suffer from overexposure with possible adverse effects on metabolism, cardiovascular control, immune function, and behavior. Also in the MR gene, variants are being identified that are associated with dysregulated autonomic, behavioral, and neuroendocrine responses. The data suggest that these MR and GR variants contribute to individual differences in resilience and vulnerability to stressors, and that these receptors therefore are potential drug targets for recovery of homeostasis and health.
应激相关精神病理学神经内分泌学中的一个基本问题是，为什么在相似的不利条件下，有些人能茁壮成长，而另一些人却会垮掉。在本论文中，我们关注盐皮质激素受体（MR）和糖皮质激素受体（GR）的变体，它们相互平衡运作，并协调参与体内平衡和健康的行为、自主神经及神经内分泌反应模式。在GR基因中，有三个单核苷酸多态性（SNP）与代谢特征和心血管参数的变化有关：ER22/23EK具有有利特征，而N363S和Bcl1具有更不利的特征。重要的是，发现N363S和Bcl1会增加对应激社会心理因素的皮质醇反应。结果，全身会因过度暴露而受到影响，可能对代谢、心血管控制、免疫功能和行为产生不利影响。同样在MR基因中，也发现了与自主神经、行为和神经内分泌反应失调相关的变体。数据表明，这些MR和GR变体导致了个体在抗压能力和对压力源易感性方面的差异，因此这些受体是恢复体内平衡和健康的潜在药物靶点。
