Corticosteroid receptor genetic polymorphisms and stress responsivity.
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.
DeRijk
Roel
R
Department of Psychiatry, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands.
de Kloet
E Ronald
ER
D000222:Adaptation, Physiological; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000235:genetics* / Q000378:metabolism; D013312:Stress, Physiological / Q000235:genetics* / Q000378:metabolism; D013315:Stress, Psychological / Q000235:genetics* / Q000378:metabolism
D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D006854:Hydrocortisone