Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0848237 (acute stress)
 4,619 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cAMP signalling pathway plays a key role in the regulation of the hypothalamic-pituitary-adrenal axis. Transcription factor CREM (cAMP response element modulator) is implicated in the modulation of a number of neuroendocrine functions. By virtue of an alternative, intronic promoter CREM generates the powerful transcriptional repressor ICER (inducible cAMP early repressor), which displays a pronounced neuroendocrine-specific expression. Here we document a remarkable induction of ICER in response to acute stress in the intermediate lobe (IL) of the pituitary gland. The induction is transient and is preceded by CREB phosphorylation. Adrenergic stimulation directs ICER induction in the IL through the activation of both beta2-adrenergic and corticotrophin-releasing hormone receptors. These receptors are positively coupled to the adenylate cyclase signalling pathway, which regulates hormone release from the IL, implicating ICER in the modulation of peptide secretion. We show that targeted ablation of the CREM gene in the mouse causes a chronic increase of beta-endorphin levels. Altered hormonal production occurs both in basal conditions and after stress. Thus, early ICER induction in the IL may be involved in the modulation of gene expression in response to stress.
 ...
PMID:The inducible cyclic adenosine monophosphate early repressor (ICER) in the pituitary intermediate lobe: role in the stress response. 1058 Aug 43

Regulation of glucocorticoid receptor (GR) levels is an important stress adaptation mechanism. Transcription factor Nfgi-a and environmentally induced Gr promoter 1 7 methylation have been implicated in fine-tuning the expression of Gr 1 7 transcripts. Here, we investigated Gr promoter 1 7 methylation and Gr 1 7 expression in adult rats exposed to either acute or chronic stress paradigms. A strong negative correlation was observed between the sum of promoter-wide methylation levels and Gr 1 7 transcript levels, independent of the stressor. Methylation of individual sites did not, however, correlate with transcript levels. This suggested that promoter 1 7 was directly regulated by promoter-wide DNA methylation. Although acute stress increased Ngfi-a expression in the hypothalamic paraventricular nucleus (PVN), Gr 1 7 transcript levels remained unaffected despite low methylation levels. Acute stress had little effect on these low methylation levels, except at four hippocampal CpGs. Chronic stress altered the corticosterone response to an acute stressor. In the adrenal and pituitary glands, but not in the brain, this was accompanied by an increase in methylation levels in orchestrated clusters rather than individual CpGs. PVN methylation levels, unaffected by acute or chronic stress, were significantly more variable within- than between-groups, suggesting that they were instated probably during the perinatal period and represent a pre-established trait. Thus, in addition to the known perinatal programming, the Gr 1 7 promoter is epigenetically regulated by chronic stress in adulthood, and retains promoter-wide tissue-specific plasticity. Differences in methylation susceptibility between the PVN in the perinatal period and the peripheral HPA axis tissues in adulthood may represent an important "trait" vs. "state" regulation of the Gr gene.
 ...
PMID:Epigenetic regulation of the glucocorticoid receptor promoter 1(7) in adult rats. 2302 26

Exposure to serious or traumatic events early in life can lead to persistent alterations in physiological stress response systems, including enhanced cross talk between the neuroendocrine and immune system. These programming effects may be mechanistically involved in mediating the effects of adverse childhood experience on disease risk in adulthood. We investigated hormonal and genome-wide mRNA expression responses in monocytes to acute stress exposure, in a sample of healthy adults (n=30) with a history of early childhood adversity, and a control group (n=30) without trauma experience. The early adversity group showed altered hypothalamus-pituitary-adrenal axis responses to stress, evidenced by lower ACTH and cortisol responses. Analyses of gene expression patterns showed that stress-responsive transcripts were enriched for genes involved in cytokine activity, cytokine-cytokine receptor interaction, chemokine activity, and G-protein coupled receptor binding. Differences between groups in stress-induced regulation of gene transcription were observed for genes involved in steroid binding, hormone activity, and G-protein coupled receptor binding. Transcription factor binding motif analysis showed an increased activity of pro-inflammatory upstream signaling in the early adversity group. We also identified transcripts that were differentially correlated with stress-induced cortisol increases between the groups, enriched for genes involved in cytokine-cytokine receptor interaction and glutamate receptor signaling. We suggest that childhood adversity leads to persistent alterations in transcriptional control of stress-responsive pathways, which-when chronically or repeatedly activated-might predispose individuals to stress-related psychopathology.
 ...
PMID:Altered Stress-Induced Regulation of Genes in Monocytes in Adults with a History of Childhood Adversity. 2709 81