Dataset Information

Environmental stressors and epigenetic control of the hypothalamic-pituitary-adrenal axis.

ABSTRACT: In this review, we provide a brief summary of several key studies that broaden our understanding of stress and its epigenetic control of the function and behavior of the hypothalamic-pituitary-adrenal (HPA) axis. Clinical and animal studies suggest a link among exposure to stress, dysregulation of the HPA axis, and susceptibility to neuropsychiatric illnesses. Recent studies have supported the notion that exposure to glucocorticoids and stress in various forms, durations, and intensities during different periods of development leads to long-lasting maladaptive HPA axis response in the brain. They demonstrate that this maladaptive response is comprised of persistent epigenetic changes in the function of HPA axis-associated genes that govern homeostatic levels of glucocorticoids. Stressors and/or disruption of glucocorticoid dynamics also target genes such as brain-derived neurotrophic factor(BDNF) and tyrosine hydroxylase(TH) that are important for neuronal function and behavior. While a definitive role for epigenetic mechanisms remains unclear, these emerging studies implicate glucocorticoid signaling and its ability to alter the epigenetic landscape as one of the key mechanisms that alter the function of the HPA axis and its associated cascades. We also suggest some of the requisite studies and techniques that are important, such as additional candidate gene approaches, genome-wide epigenomic screens, and innovative functional and behavioral studies, in order to further explore and define the relationship between epigenetics and HPA axis biology. Additional studies examining stress-induced epigenetic changes of HPA axis genes, aided by innovative techniques and methodologies, are needed to advance our understanding of this relationship and lead to better preventive, diagnostic, and corrective measures.

SUBMITTER: Lee RS

PROVIDER: S-EPMC4428760 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Environmental stressors and epigenetic control of the hypothalamic-pituitary-adrenal axis.

Lee Richard S RS Sawa Akira A

Neuroendocrinology 20141118 4

In this review, we provide a brief summary of several key studies that broaden our understanding of stress and its epigenetic control of the function and behavior of the hypothalamic-pituitary-adrenal (HPA) axis. Clinical and animal studies suggest a link among exposure to stress, dysregulation of the HPA axis, and susceptibility to neuropsychiatric illnesses. Recent studies have supported the notion that exposure to glucocorticoids and stress in various forms, durations, and intensities during ...[more]

PMID: 25427939

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Project description:The endogenous opioid system is involved in modulating a number of behavioral and physiological systems, including the hypothalamic-pituitary-adrenal (HPA) axis. In humans, a functional variant in the OPRM1 gene (OPRM1 A118G) is associated with a number of outcomes, including attenuated HPA axis responses to stress. A nonsynonymous variant (OPRM1 C77G) in the rhesus macaque has been shown to have similar effects in vivo to the human variant. The current study investigated whether OPRM1 C77G influences HPA axis response to stress in rhesus macaques. We analyzed plasma adrenocorticotropic hormone (ACTH) and cortisol levels measured in response to three different stressors: (1) maternal separation in infant subjects at 6 months of age, (2) acute ethanol administration in adolescent subjects at 4 years of age, and (3) postpartum HPA axis function in adult rhesus macaque females. For the maternal separation paradigm, ACTH and cortisol levels were determined at baseline as well as peak levels during each of 4 consecutive separation episodes. For the acute ethanol administration paradigm, hormone levels were determined at baseline and again at 5 min, 10 min, and 60 min following the ethanol infusion. For postpartum sampling, hormone levels were determined at postpartum days 7, 14, 21, 30, 60, 90, 120, and 150. Infants carrying the 77G allele exhibited lower levels of cortisol across all 4 separation episodes. Furthermore, adolescents carrying the 77G allele exhibited lower cortisol levels at 5 and 10 min following acute ethanol administration. Adult females with prior reproductive experience and who carry the 77G allele exhibited lower cortisol levels across the postpartum period. No significant genotype effects were found for ACTH, although there were some trends for lower ACTH levels in 77G allele carriers. These data are consistent with human studies that have demonstrated attenuated cortisol responses to stress among carriers of the OPRM1 118G allele, lending further support to the argument that the rhesus and human allelic variants are functionally similar. Our results also suggest that OPRM1 variation may influence coping style, as well as alcohol-induced and postpartum levels of HPA axis activity and, as such, may modify vulnerability to alcohol use disorders and postpartum depression.

Dataset Information

Environmental stressors and epigenetic control of the hypothalamic-pituitary-adrenal axis.

Publications

Environmental stressors and epigenetic control of the hypothalamic-pituitary-adrenal axis.

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