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

Previous studies have indicated that acute stress in vivo or ovine corticotropin releasing hormone (oCRH) in vitro, releases both beta-lipotropin (beta-LPH) and beta-endorphin (beta-END) from the anterior lobe, with beta-END predominating over beta-LPH by 2:1. However, repeated stress shifts this ratio to proportionately more beta-LPH released with re-stress or oCRH in vitro. Alternative hypotheses were that the glucocorticoids released during stress altered the processing of proopiomelanocortin (POMC) or that the increased biosynthetic drive resulted in an inability of the processing enzymes to keep pace with biosynthesis. To distinguish between these alternatives, adrenalectomy studies were performed. Following removal of glucocorticoid negative feedback there is greatly increased secretion of beta-END-IR from anterior lobe corticotrophs with a subsequent increase in biosynthetic drive. Under these conditions of increased biosynthetic drive in the absence of steroids, the corticotroph secretes primarily beta-LPH, suggesting that increased biosynthetic drive alters the posttranslational processing rate of POMC.
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PMID:Adrenalectomy increases beta-lipotropin secretion over beta-endorphin secretion from anterior pituitary corticotrophs. 260 76

Successful adaptation to stress is a prerequisite for the survival of all organisms living in an environment in which noxious stimuli are constantly present. Higher organisms, including human beings, have developed complex mechanisms to tolerate the myriad of insults that occur to cellular constituents and organ systems after trauma with its resultant blood loss and tissue injury. Surgical stress can be conceptualized in this context, and it is therefore not surprising that human beings have developed an array of integrated stress-response axes that work in concert to return the host to a sustainable homeostatic plateau. The most important aspects of these axes are depicted in Figure 24. Surgical stress activates the higher cortical center of the brain and the spinal and baroreceptor reflexes that stimulate the hypothalamus to secrete CRH. CRH stimulates the release of ACTH from the pituitary gland, which causes the release of glucocorticoids from the adrenal cortex. Simultaneously, in a parallel fashion, surgical stress activates the sympathetic system to release catecholamines. Glucocorticoids and catecholamines are the major effectors of stress adaptation and interact at multiple levels in a synergistic fashion. They bind to specific receptors that are present in virtually every organ, although the number and affinity of a given tissue's receptor vary dramatically for individual ligands. Receptor occupancy results in short-term and long-term effects that ultimately improve the host's prospects of tolerating the stressful event. The short-term effects result in rapid actions, such as cardiovascular and metabolic responses that benefit the host in a "fight or flight" reaction. The long-term effects generally occur through alterations in gene transcription that prepare the host for, or adapt the host to, repetitive or chronic stress. Changes in the phosphorylation state of intracellular proteins are a common mode of action for both the short-term and long-term responses. These stress-responsive proteins have an enormous functional capacity: they alter enzymatic pathways, modulate hormone levels, and act as transcription factors to modify the expression of stress-responsive genes. During the last decade considerable progress has been made in explaining the complex signal transduction pathways mediating these responses. The importance of the HSPs in the host response to acute stress and their intimate association with activation of the HPA axis and sympathetic nervous system have recently been appreciated. The HSPs are likely to be induced early during organ rejection or ischemia and thus serve as diagnostic indicators.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Endocrine and molecular responses to surgical stress. 804 59

The contribution of the magnocellular vasopressinergic system to the regulation of ACTH secretion was studied by analysis of hypothalamic-adrenal axis function in rats subjected to water deprivation for 48 h. Water deprivation resulted in marked increases in plasma osmolarity and vasopressin (VP) levels and hypothalamic VP mRNA and immunoreactive (ir) VP in magnocellular neurons. While CRH mRNA levels in the paraventricular nucleus were decreased, irCRH accumulation in paraventricular nucleus neurons after colchicine treatment was normal or increased. Similarly, the irCRH content in the median eminence and its release under stress were similar in control and water-deprived rats. While basal plasma ACTH levels were similar in both groups (34.5 +/- 3.8 and 39.8 +/- 3.3 pg/ml), levels stimulated by CRH injection (10 micrograms, i.v.) or 15-min immobilization stress were reduced by 47% (P < 0.01) and 43% (P < 0.05), respectively, in water-restricted rats. The decreased ACTH responses were not prevented by injection of CRH (7.5 micrograms/day, sc) during the period of water deprivation. In contrast to the ACTH responses, basal and CRH-stimulated plasma corticosterone levels were significantly elevated (P < 0.001), and the responses to acute stress were normal. The inhibition of ACTH secretion was not due to increased glucocorticoid feedback, since similar blunted ACTH responses to acute immobilization stress were observed in adrenalectomized rats receiving corticosterone replacement. Despite similar levels of pituitary POMC mRNA, pituitary ACTH content was reduced in water-deprived rats, suggesting a posttranscriptional inhibition of POMC synthesis or processing. The data demonstrate that osmotic activation of the magnocellular VP system is accompanied by reduced responsiveness of the corticotrophs, an effect that is not due to increased glucocorticoid feedback or hypothalamic CRH deficiency. These findings suggest that the magnocellular vasopressinergic system does not play an important role in the regulation of ACTH secretion during chronic osmotic stimulation.
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PMID:Regulation of the hypothalamic-pituitary-adrenal axis during water deprivation. 838 Mar 75

Previous studies have demonstrated that acute stress or ovine corticotropin-releasing hormone (oCRH) in vivo, or oCRH in vitro, stimulates release of beta-endorphin over beta-lipotropin from anterior pituitary corticotropes. This occurs despite the predominance of beta-lipotropin in corticotrope peptide stores. In vitro studies with primary anterior pituitary cultures suggested that chronic exposure to oCRH results in a shift towards more beta-lipotropin secretion into the media than with short-term exposure. The current studies explored whether increased secretory drive in vivo results in a similar shift towards more beta-lipotropin. We used removal of glucocorticoids by adrenalectomy or metyrapone blockade of corticosterone synthesis, to stimulate endogenous secretion of CRH and vasopressin. Both treatments resulted in shifts of the ratio of beta-endorphin: beta-lipotropin in plasma of experimental animals in comparison to the sham-treated control rats. In vitro testing with oCRH of anterior lobe cultures from adrenalectomized or metyrapone-treated rats demonstrated similar effects of these treatments on the ratio of beta-endorphin:beta-lipotropin. These changes occurred despite similar ratios of beta-endorphin:beta-lipotropin in anterior pituitary peptide stores.
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PMID:Altered ratios of beta-endorphin: beta-lipotropin released from anterior lobe corticotropes with increased secretory drive. I. Effects of diminished glucocorticoid secretion. 848 40

Double staining in situ hybridization studies have shown that angiotensin II (AII) type 1 receptors (AT1) in the hypothalamic paraventricular nucleus (PVN) are located primarily in corticotropin releasing hormone (CRH) neurons of the parvicellular subdivision. The purpose of these studies was to investigate the role of AII regulating the hypothalamic-pituitary adrenal (HPA) axis, by correlating AT1 receptor expression levels in the PVN with the known changes in activity of the HPA axis under different stress paradigms, and manipulation of circulating glucocorticoids. AT1 receptor mRNA was measured by in situ hybridization using 35S-labelled cRNA probes and AII binding by autoradiography using 125I[Sar1,Ile8]AII in slide mounted hypothalamic sections. AT1 receptor mRNA levels and AII binding in the PVN were reduced by about 20% 18 h after adrenalectomy remaining at these levels up to 6 days after. This effect was prevented by corticosterone administration in the drinking water, or dexamethasone injection (100 mg, s.c., daily). Conversely, dexamethasone injection in intact rats caused a 20% increase in AT1 receptor mRNA in the PVN. AT1 receptor mRNA and binding in the PVN increased 4 h after exposure to stress paradigms associated with activation of the HPA axis (immobilization for 1 h, or i.p. injection of 1.5 M NaCl), and remained elevated after repeated daily stress for 14 days. Unexpectedly, two osmotic stress models associated with inhibition of the HPA axis (60 h water deprivation or 12 days of 2% saline intake) also resulted in increased AT1 receptor mRNA levels and AII binding in the parvicellular PVN. In intact rats, the stimulatory effect of acute stress on AT1 receptor mRNA in the PVN was significantly enhanced by dexamethasone administration (100 micrograms, s.c., 14 h and 1 h prior to stress), while in adrenalectomized rats, with or without glucocorticoid replacement, stress reduced rather than increased, AT1 receptor mRNA. Dexamethasone, 100 micrograms, injected sc within 1 min the beginning of immobilization in adrenalectomized rats, increased AT1 receptor mRNA in the PVN to levels significantly higher than those after dexamethasone alone, indicating that the stress induced glucocorticoid surge is required for the stimulatory effect of stress on AT1 receptor mRNA. The data suggest that AT1 receptor expression in the PVN is under dual control during stress: stress-activated inhibitory pathways and the stimulatory effect of glucocorticoids. The lack of specificity of the changes in AT1 receptor expression in the PVN following stressors with opposite effects on ACTH secretion (osmotic and physical-psychological stress) does not support a role for AII as a major determinant of the response of the HPA axis during stress.
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PMID:Increased expression of type 1 angiotensin II receptors in the hypothalamic paraventricular nucleus following stress and glucocorticoid administration. 856 20

The effects of acute stress on various indices of sympatho-adrenal, sympathoneural functions and hypothalamic-pituitary-adrenal (HPA) axis were examined both at central and peripheral sites in healthy, intact male Fischer 344/N rats of increasing age. Extracellular fluid (ECF) levels of norepinephrine (NE), its metabolites dihydroxyphenylglycol (DHPG), and methoxyhydroxyphenylglycol (MHPG), and of the dopamine metabolite dihydroxyphenylacetic acid (DOPAC), were measured 24 h after implantation of a microdialysis probe in the paraventricular nucleus (PVN) of the hypothalamus, and samples collected at 30-min. intervals during immobilization (IMMO). ECF levels of NE, DHPG, MHPG, and DOPAC were at baseline similar in both age groups, and all increased significantly in response to IMMO. The IMMO-induced increases in ECF levels of NE and MHPG were, however, significantly smaller in old than in young rats. Plasma levels of the dihydroxyphenylalanine (DOPA), -NE, epinephrine (EPI), DHPG, MHPG, dopamine (DA), DOPAC and HVA, were determined in different groups of young and old rats, cannulated in the tail artery, at baseline, and after 5, 30, 60, and 120 min of IMMO. Basal levels of DOPA, DHPG, MHPG, DA, DOPAC, HVA, NE and EPI were significantly higher in old than in young rats, and increased in plasma during IMMO. However, the magnitude of the increase in the majority of these compounds was significantly smaller in old than in young rats. Basal plasma levels of ACTH were similar among age groups, and basal plasma levels of corticosterone showed a significant aging-associated decline. Two i.v. doses (2 and 20 micrograms/kg BW) of rat CRF elicited significantly greater and delayed ACTH, and greater corticosterone responses in older rats, consistent with the pattern encountered in hypothalamic CRF deficiency. An i.v. injection of ACTH evoked lower corticosterone responses in the older (18 and 24 month old) than in the younger (2 and 8 month old) groups of rats, consistent with secondary adrenocortical atrophy in older animals. Steady-state mRNA levels of mineralocorticoid and glucocorticoid receptors were significantly decreased in the hippocampus of the 8-, 18-, and 24-month-old rats, compatible with maturational rather than senescent changes. CRF mRNA levels in the paraventricular nucleus of the hypothalamus, and levels of POMC mRNA in the anterior pituitary were significantly reduced with age. In conclusion, in this strain of rats, aging is associated with diminished responsiveness of central, and peripheral catecholaminergic systems to acute stress, and progressive hypothalamic CRH deficiency.
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PMID:Aging is associated in the 344/N Fischer rat with decreased stress responsivity of central and peripheral catecholaminergic systems and impairment of the hypothalamic-pituitary-adrenal axis. 859 25

The expression of corticotropin releasing hormone (CRH) in the hypothalamic paraventricular nucleus (PVN) and CRH receptor mRNA in the PVN and anterior pituitary was studied during development of adjuvant-induced arthritis in Piebald-Viral-Glaxo rats, using in situ hybridization techniques. As previously shown with i.p. hypertonic saline injection, basal and immobilization stress-stimulated CRH mRNA levels in the PVN were significantly lower than in controls 14 days after adjuvant injection. However, 7 days after injection, preceding the onset of inflammation, the increase of CRH mRNA following immobilization was significantly higher than in control rats. In contrast to other chronic stress paradigms, inflammation stress failed to induce type-1 CRH receptor (CRH-R1) mRNA in the PVN, either at 7 days, or at 14 days after adjuvant injection, when inflammation is present. The ability of acute immobilization to induce CRH-R1 mRNA in the PVN was not affected 14 days after adjuvant injection but parallel to the CRH peptide mRNA response it was markedly potentiated at 7 days. Pro-opiomelanocorpin (POMC) mRNA levels in the anterior pituitary increased significantly 14 days after adjuvant injection, and they were unaffected by 1 h immobilization. While CRH binding in the pituitary decreased significantly 14 days after adjuvant injection, CRH-R1 mRNA was unchanged. This study shows biphasic hypothalamic responses to acute stress during development of adjuvant-induced arthritis, with enhanced CRH peptide and CRH-R1 mRNAs responses at 7 days, preceding the onset of inflammation, and blunted CRH mRNA responses at 14 days at the height of the inflammatory response. The lack of CRH receptor expression in the PVN in this model of chronic inflammation stress associated to low hypothalamic CRH peptide levels supports the view that positive feedback regulation by CRH is necessary to maintain enhanced CRH expression during chronic stress.
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PMID:Differential regulation of hypothalamic pituitary corticotropin releasing hormone receptors during development of adjuvant-induced arthritis in the rat. 916 7

In this review, we have described the function of MR and GR in hippocampal neurons. The balance in actions mediated by the two corticosteroid receptor types in these neurons appears critical for neuronal excitability, stress responsiveness, and behavioral adaptation. Dysregulation of this MR/GR balance brings neurons in a vulnerable state with consequences for regulation of the stress response and enhanced vulnerability to disease in genetically predisposed individuals. The following specific inferences can be made on the basis of the currently available facts. 1. Corticosterone binds with high affinity to MRs predominantly localized in limbic brain (hippocampus) and with a 10-fold lower affinity to GRs that are widely distributed in brain. MRs are close to saturated with low basal concentrations of corticosterone, while high corticosterone concentrations during stress occupy both MRs and GRs. 2. The neuronal effects of corticosterone, mediated by MRs and GRs, are long-lasting, site-specific, and conditional. The action depends on cellular context, which is in part determined by other signals that can activate their own transcription factors interacting with MR and GR. These interactions provide an impressive diversity and complexity to corticosteroid modulation of gene expression. 3. Conditions of predominant MR activation, i.e., at the circadian trough at rest, are associated with the maintenance of excitability so that steady excitatory inputs to the hippocampal CA1 area result in considerable excitatory hippocampal output. By contrast, additional GR activation, e.g., after acute stress, generally depresses the CA1 hippocampal output. A similar effect is seen after adrenalectomy, indicating a U-shaped dose-response dependency of these cellular responses after the exposure to corticosterone. 4. Corticosterone through GR blocks the stress-induced HPA activation in hypothalamic CRH neurons and modulates the activity of the excitatory and inhibitory neural inputs to these neurons. Limbic (e.g., hippocampal) MRs mediate the effect of corticosterone on the maintenance of basal HPA activity and are of relevance for the sensitivity or threshold of the central stress response system. How this control occurs is not known, but it probably involves a steady excitatory hippocampal output, which regulates a GABA-ergic inhibitory tone on PVN neurons. Colocalized hippocampal GRs mediate a counteracting (i.e., disinhibitory) influence. Through GRs in ascending aminergic pathways, corticosterone potentiates the effect of stressors and arousal on HPA activation. The functional interaction between these corticosteroid-responsive inputs at the level of the PVN is probably the key to understanding HPA dysregulation associated with stress-related brain disorders. 5. Fine-tuning of HPA regulation occurs through MR- and GR-mediated effects on the processing of information in higher brain structures. Under healthy conditions, hippocampal MRs are involved in processes underlying integration of sensory information, interpretation of environmental information, and execution of appropriate behavioral reactions. Activation of hippocampal GRs facilitates storage of information and promotes elimination of inadequate behavioral responses. These behavioral effects mediated by MR and GR are linked, but how they influence endocrine regulation is not well understood. 6. Dexamethasone preferentially targets the pituitary in the blockade of stress-induced HPA activation. The brain penetration of this synthetic glucocorticoid is hampered by the mdr1a P-glycoprotein in the blood-brain barrier. Administration of moderate amounts of dexamethasone partially depletes the brain of corticosterone, and this has destabilizing consequences for excitability and information processing. 7. The set points of HPA regulation and MR/GR balance are genetically programmed, but can be reset by early life experiences involving mother-infant interaction. 8. (ABSTRACT TRUNCATED)
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PMID:Brain corticosteroid receptor balance in health and disease. 962 55

It is now established that communication between the CNS and the immune system is bidirectional, that endocrine factors can alter immune function and that immune responses can alter both endocrine and CNS responses. In many respects CNS and endocrine responses to acute inflammation are similar to the changes associated with acute stress exposure. In contrast, during chronic inflammation associated with adjuvant induced arthritis (AA), although circulating levels of corticosterone are increased, the peptidergic regulation of the hypothalamus is different from that seen during acute stress. As the disease progresses, a paradoxical reduction occurs in CRH mRNA in the paraventricular nucleus (PVN), whereas PVN AVP mRNA increases. These data suggest that there is increased expression of AVP mRNA within the CRH cells of the PVN with an increased emphasis on AVP regulation of HPA output. Additionally, HPA function is altered during chronic inflammation such that responses to psychological stress (i.e. restraint) are significantly dampened, while responses to further inflammatory challenges are maintained. These data suggest that alterations in PVN peptide colocalization may be important in regulating the progression of peripheral inflammatory responses and that the effects of inflammation on the hypothalamus alter stress-responsive systems. In addition to the AA model, we have similarly observed alterations in PVN peptide mRNA expression with disease onset in the murine MRL lpr/lpr and MRL +/+ model of SLE. Disease onset in murine SLE is spontaneous and does not rely on exogenous application of adjuvant; however, decreased levels of CRH in the PVN were observed from early disease onset in this animal model. It is suggested that alterations in CRH regulation in response to either acute or chronic inflammation may contribute as etiological factors to both psychiatric (i.e. neuropsychiatric SLE) and stress-related disease.
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PMID:Inflammatory disease as chronic stress. 962 87

Acute stress causes biphasic changes in corticotropin releasing hormone (CRH) receptor mRNA expression with an early decrease followed by an increase. However, in the absence of glucocorticoids in adrenalectomized rats, stress results in prolonged CRH receptor (CRH-R) mRNA loss, suggesting that interactions between glucocorticoids and hypothalamic factors are critical for regulation of CRH receptor mRNA. To address this question, CRH binding, type-1 CRH-R mRNA, POMC mRNA and POMC hnRNA expression were measured by binding autoradiography and in situ hybridization in pituitaries from intact and adrenalectomized rats. CRH-R mRNA decreased by 59% 5 h after injection of corticosterone (10 mg s.c.) and returned to basal levels by 18 h, a time when plasma corticosterone concentrations were still elevated, and CRH binding and POMC hnRNA were significantly reduced. Elevations in plasma corticosterone in the range of acute stress by injection of 2 mg s.c. caused CRH-R mRNA expression to return to near basal values by 6 h, after a 52% and 39% decrease at 2 h and 4 h. More transient changes were seen after a single injection of CRH (1 microg), with a 44% decrease in CRH-R mRNA and a 175% increase in POMC hnRNA by 2 h, returning to basal values by 4 h. The transient effect of CRH was not due to clearance of CRH from the circulation or receptor desensitization since CRH receptor mRNA expression also recovered after injection of a higher dose (10 microg) or repeated injections of CRH which caused sustained increases in plasma CRH and pituitary POMC hnRNA levels. CRH injection in adrenalectomized rats decreased CRH-R mRNA for up to 6 h, suggesting that glucocorticoids are permissive for the recovery of CRH-R mRNA. Supporting this hypothesis, simultaneous injection of corticosterone and CRH restored CRH-R mRNA expression by 4 h, and increased CRH binding 4 h and 6 h after injection. The data show that interaction between CRH and glucocorticoids counteracts individual inhibitory effects of these regulators alone, and that such effects are likely to contribute to the regulatory pattern of pituitary CRH receptors during acute stress.
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PMID:Interaction between glucocorticoids and corticotropin releasing hormone (CRH) in the regulation of the pituitary CRH receptor in vivo in the rat. 966 50


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