Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurotransmitter-neuroendocrine and cardiovascular responses to the administration of a psychologically stressful mixed-model test (Mental Arithmetic, Stroop Color Word Interference Task, Trier Social Stress Test) were examined in 20 male peripubertal subjects affected by anxiety disorder (group A: 14 with generalized anxiety disorder, 6 with generalized anxiety disorder and separation anxiety disorder) and 20 junior school adolescents, matched for age, without overt psychological disorders (group B). Plasma levels of norepinephrine (NE), epinephrine (EPI), adrenocorticotropic hormone (ACTH), beta-endorphin (beta-EP), cortisol (CORT), growth hormone (GH), prolactin (PRL) and testosterone (Te) were measured immediately before the beginning of the tests and 30 min later at their end. Mean prestress values of GH, PRL, beta-EP and ACTH were significantly higher in anxious subjects than in controls. There was no difference in NE, EPI, CORT and Te prestress levels in the two groups. After the psychological stress session NE, GH and Te concentrations increased significantly in anxious subjects (A), but not in controls. In contrast, beta-EP and PRL decreased significantly during the psychological stress session in anxious subjects, and were unaffected by stress in the subjects without anxiety. No significant changes were found in ACTH, CORT and EPI during the challenge either in anxious subjects or in controls, which may be attributed to the late time of poststress blood sampling. In contrast to controls, heart rate and systolic blood pressure increased significantly in anxious subjects after psychological stress testing. Our data support the hypothesis that the hyperactivity of the noradrenergic system in response to stress is associated with anxiety disorders in adolescents and might influence the responses of GH and Te. High prestress basal values of stress hormones seem to be induced in anxious subjects by the anticipation of the task or by a persistent hyperactivity of the noradrenergic system. Further studies are needed to investigate in more detail the involvement of the HPA axis in anxious adolescents by a more refined resolution of time points of blood sampling.
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PMID:Neuroendocrine responses to psychological stress in adolescents with anxiety disorder. 1094 Jul 63

In order to investigate the potential influence of stress as a component of the repeat breeding syndrome, the adrenocortical capacity for steroid production was evaluated in ovariectomised dairy heifers. In repeat breeder heifers (RBH), marginally elevated plasma progesterone levels during oestrus, so-called suprabasal progesterone levels, have earlier been measured and are believed to impair fertility. The aim was to distinguish if this progesterone could be of extra-gonadal or in this case, adrenal origin. Baseline levels of plasma cortisol and progesterone were determined as well as the corresponding response after induced acute stress in the form of an adrenocorticotropin (ACTH)-challenge. Comparisons were made between strictly selected RBH, n=5 and virgin heifers (VH), n=5 of the Swedish Red and White breed. The heifers were used as their own pre-challenge controls in a 2-day trial. On the control day, saline was injected i.v. and on the treatment day, a synthetic analogue of ACTH (60 microg Synachten(R)). Via a jugular vein catheter, blood samples were collected every 30 min for 6 h each day of the experiment. Analyses for plasma progesterone and cortisol were made. RBH had a significantly higher (P<0.01) pretreatment baseline cortisol level (10.1+/-2.3 nmol l(-1)) than VH (2.6+/-0.2 nmol l(-1)). Moreover, the cortisol response after stimuli was stronger in RBH than VH, especially concerning total hormone production (P<0. 001), but there was also a tendency towards higher peak values (P=0. 06) and longer duration of significantly increased hormone concentrations (P=0.08). Progesterone concentrations, however, did not differ between the groups. Both baseline levels (P=0.25) and posttreatment production (P=0.45) were of the same magnitude in RBH and VH. In conclusion, the study could not confirm that suprabasal progesterone concentrations during oestrus in RBH derive from the adrenal glands. Still, apparent differences were found in adrenocortical activity when ovariectomised heifers, VH and RBH, were subjected to an ACTH-challenge. It is suggested that a sustained adrenal stimulation associated with environmental or social stress could be one factor in the repeat breeding syndrome.
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PMID:Effect of ACTH-challenge on progesterone and cortisol levels in ovariectomised repeat breeder heifers. 1096 41

In patients with major depression, abnormalities in baseline cortisol secretion and resistance to negative feedback are well established. However, it is unclear if patients with major depression have alterations in the hypothalamic-pituitary-adrenal (HPA) response to stressors. While other challenges to the HPA axis have used endocrine stimuli such as insulin-induced hypoglycemia, we now report of the response to a social stressor in patients with major depression and matched control subjects. We used the Trier Social Stress Test (TSST), a public speaking task followed by mental arithmetic challenge in front of a panel of judges. The results suggest that depressed patients manifest normal cortisol response to a social stressor, despite increased pre-stressor plasma cortisol. However, the beta-endorphin response to the TSST was significantly smaller in the depressed patients compared to matched controls. These data are similar to data found with exogenous corticotropin-releasing-hormone challenge studies and suggest that elevated baseline cortisol can modulate the pituitary corticotroph response to a stressor, but that changes in adrenal sensitivity to ACTH result in a robust cortisol response to this stressor.
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PMID:Hormonal evidence for altered responsiveness to social stress in major depression. 1098 68

Beta-endorphin is an endogenous opioid peptide that is released during stress and has been associated with many physiological functions. In this experiment beta-endorphin deficient mice were used to study the role of endorphins in the acute physiological and behavioral responses to a social conflict, as well as their role in social stress-induced changes in sleep. Adult male beta-endorphin deficient and wild type mice were subjected to the stress of a 1 h social conflict with an aggressive dominant conspecific. After the conflict, the beta-endorphin deficient mice had higher corticosterone levels but the peak increase in body temperature was not different from that in wild type animals. In fact, body temperature returned to baseline levels faster in the beta-endorphin deficient mice. During their interaction with the aggressive conspecific several of the beta-endorphin deficient mice showed clear signs of counter aggression whereas this was not seen in any of the wild type mice. Overall, the beta-endorphin deficient mice and wild type mice had fairly similar sleep patterns under baseline conditions and also showed similar amounts of NREM sleep, REM sleep and EEG slow-wave energy after the social conflict. In addition, no differences were found in the sleep patterns of mice that showed counter aggression and mice that did not. In conclusion, the results suggest that beta-endorphin modulates the acute endocrine, thermoregulatory and behavioral response to a social conflict but the data do not support a major role for beta-endorphin in the regulation of sleep or social stress-induced alterations in sleep.
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PMID:Beta-endorphin modulates the acute response to a social conflict in male mice but does not play a role in stress-induced changes in sleep. 1283 11

A polymorphism in the mu-opioid receptor (MOR) (A118G) has been shown to increase beta-endorphin binding affinity, theoretically placing greater inhibitory tone on hypothalamic corticotropin-releasing hormone (CRH) neurons. We hypothesized that the minor allele (G) would predict cortisol responses to both pharmacological (naloxone) and psychological (stress) activation of the hypothalamic-pituitary-adrenal (HPA) axis. Healthy subjects (mean age 25.2 years, SD 9.2 years) completed a naloxone challenge (n=74) and/or the modified Trier Social Stress Test (TSST) (n=86). For the naloxone challenge, two baseline blood samples were obtained. Then, five increasing doses of i.v. naloxone were administered at 30-min intervals and 12 additional blood samples were collected at 15-min intervals. The TSST consisted of 5-min of public speaking and 5-min of mental arithmetic exercises. Three baseline and five post-TSST blood samples were drawn. Both the naloxone and TSST groups had significant adrenocorticotropin (ACTH) and cortisol responses to their respective challenges (P<0.001). There were no differences in baseline ACTH, baseline cortisol, or ACTH response by genotype in either the naloxone or the TSST group. Among subjects expressing a G allele, there was a higher cortisol response to naloxone (P=0.046), but a lower cortisol response to the TSST (P=0.044). In conclusion, the minor allele (G) was associated with a robust cortisol response to naloxone blockade, but a blunted response to psychosocial stress. We speculate that increased opioid avidity of the minor allele receptor contributes to the differential response to naloxone vs stress.
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PMID:The mu-opioid receptor polymorphism A118G predicts cortisol responses to naloxone and stress. 1612 58

The present study was designed to determine whether stress hormones and subjective responses to a psychological stressor were different in nonalcoholic offspring from families with a history of alcohol dependence (family history positive, FHP) than in nonalcoholic offspring without a family history of alcohol dependence (family history negative, FHN). Forty-five healthy subjects (17 FHP, 28 FHN), between the ages of 18 and 29 years, completed the Trier Social Stress Test (TSST). The TSST consisted of 5 min of public speaking followed by 5 min of mental arithmetic. Three baseline and five post-TSST blood samples were drawn. Pre- and post-TSST self-report measures of anxiety were obtained. Cortisol, adrenocorticotropin (ACTH), and prolactin significantly increased in response to the TSST in the entire study sample (F(1,187)=70.22, p<0.001, F(1,143)=33, p<0.001, and F(1,134)=14.37, p<0.001, respectively). Cortisol responses were influenced by an interaction between racial composition and family history of alcoholism (F(1,57)=4.50, p=0.038). Among Caucasian subjects, FHP subjects had greater cortisol response to the TSST compared to FHN subjects (F(1,57)=4.45, p=0.039). No family history effect was identified in African-American subjects. Adrenocorticotropin responses did not differ between FHP and FHN subjects. Adrenocorticotropin response was positively associated with baseline ACTH levels in FHN subjects (t=5.02, p=or<0.001), but not in FHP subjects. Prolactin responses did not differ between FHP and FHN subjects. Anxiety response scores (post-TSST scores minus pre-TSST scores) were higher in FHP subjects compared with FHN subjects (z=-2.67, p=0.007). In addition, anxiety response scores were positively associated with cortisol response levels to the TSST in FHN subjects (t=4.52, p<0.001). In contrast, anxiety responses were negatively associated with cortisol responses in FHP subjects (t=-2.30, p=0.024). Our findings are consistent with theories that greater reactivity to stress is associated with greater risks for alcoholism. Furthermore, the findings suggest that the association between the hypothalamic-pituitary-adrenal axis hormonal response and the subjective perception of stress might be deranged in offspring of alcoholics.
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PMID:Hormonal responses to psychological stress and family history of alcoholism. 1655 44

The present study was designed to determine whether there are gender differences in hormonal response patterns to HPA axis activation. To this end, two methods of activating the HPA axis were employed: a standardized psychological stress test and a pharmacological challenge. Healthy subjects (mean age 23.4 years, SD 7.0 years) completed a naloxone challenge and/or the modified Trier Social Stress Test (TSST). For the naloxone challenge, two baseline blood samples were obtained. Placebo was then administered (0 min), followed by increasing doses of intravenous naloxone (50, 100, 200 and 400 microg/kg) at 30-min intervals. Post-placebo blood samples were collected at 15-min intervals for 180 min. The TSST consisted of 5 min of public speaking followed by 5 min of mental arithmetic exercises. Three baseline and five post-TSST blood samples were drawn. Eighty subjects (53 male, 27 female) underwent the TSST. Following the psychological stressor, adrenocorticotropin (ACTH) and cortisol responses were significantly greater in male subjects compared to female subjects (z=-2.34, p=0.019 and z=-2.12, p=0.034, respectively). Seventy-two subjects (52 male, 20 female) underwent HPA axis activation induced by naloxone. In contrast to the TSST, cortisol responses to the naloxone challenge were significantly greater in female subjects compared to male subjects (z=4.11, p<0.001). Forty-one subjects (25 male, 16 female) completed both the TSST and naloxone challenge. In this subset, ACTH and cortisol responses to the TSST did not differ significantly by gender, although the effect size was moderate to large. Adrenocorticotropin and cortisol responses to the naloxone challenge were significantly greater in female subjects compared to male subjects (z=2.29, p=0.022 and z=4.34, p<0.001, respectively). In summary, male subjects had greater HPA axis responses to a psychological stressor than female subjects, and females had greater hormonal reactivity than males to pharmacological stimulation with naloxone. Such differences are of interest as potential contributors to gender differences in health risks.
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PMID:Gender differences in hypothalamic-pituitary-adrenal (HPA) axis reactivity. 1661 15

Prolonged social subjugation produces physiological indices of chronic stress in rats. In the current study, we examined the impact of social stress on glutamic acid decarboxylase (GAD) isoforms, corticotropin-releasing hormone (CRH) and vasopressin mRNA expression in forebrain stress circuitry, using the visible burrow system model of dominance-subordination. Subordinate male rats develop behavioral and neuroendocrine changes consistent with exposure to chronic stress, including marked loss of body weight and elevation of basal plasma corticosterone relative to dominant rats. Forebrain GAD65, GAD67, CRH and vasopressin mRNA expression in central stress-regulatory circuits were examined by in situ hybridization. Elevated CRH mRNA was observed in the oval nucleus of the bed nucleus of the stria terminalis (BST) of subordinate males. In contrast, GAD67 expression was decreased in the interfascicular nucleus of the BST in both the subordinate and dominant rats compared to non-burrow control rats. No changes in CRH, GAD or vasopressin were observed in amygdaloid nuclei, other BST nuclei or in the hypothalamic paraventricular nucleus. Collectively, these data suggest that exposure to the visible burrow system attenuates BST GAD expression regardless of social status, whereas the enhanced physiological responses to social stress seen in subordinates may be associated with enhanced CRH expression in the oval nucleus of the BST.
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PMID:Chronic social stress in the visible burrow system modulates stress-related gene expression in the bed nucleus of the stria terminalis. 1694 12

The aim of the present study was to determine the effect of social crowding stress and significance of nitric oxide (NO) and prostaglandins (PG) generated by constitutive and inducible nitric oxide synthase (NOS) and cyclooxygenase (COX) in the stimulation of hypothalamic-pituitary-adrenal (HPA) axis by cholinergic muscarinic receptor agonist carbachol. Inhibitors of neuronal NOS (nNOS) L-NNA, general NOS L-NAME and inducible NOS (iNOS) aminoguanidine, as well as inhibitors of COX-1, piroxicam, and COX-2, compound NS-398 were administered 15 min prior to carbachol to control or crowded rats (24 rats in cage for 7, during 3 and 7 days). In stressed rats L-NAME, L-NNA and aminoguanidine significantly intensified the carbachol-induced ACTH and corticosterone secretion, like in control rats. Piroxicam, markedly decreased the carbachol-induced ACTH and corticosterone response under either basal or stress conditions. Compound NS-398 did not markedly alter the carbachol-induced HPA response in control and stressed rats. Crowding stress (3 days) significantly impaired the i.c.v. prostaglandin E(2)-induced ACTH response. Corticotropin releasing hormone (CRH) receptor antagonists, alpha-helical CRH [9-14], given i.c.v. did not alter the PGE(2)-evoked corticosterone response in either control or stressed rats, indicating that hypothalamic CRH is not involved in the PGE(2)-induced central stimulation of HPA axis. In control rats L-NAME considerably enhanced, while L-arginine, a physiological NOS substrate, abolished the PGE(2)-induced ACTH and corticosterone response. In stressed rats this NOS blocker significantly increased and L-Arg reduced the stimulatory effect of PGE(2) on ACTH and corticosterone secretion. The carbachol-induced corticosterone response was significantly increased by pretreatment with nNOS inhibitor L-NNA and was considerably reduced by indomethacin, a general COX inhibitor. Pretreatment with both antagonists left the carbachol-induced corticosterone level unchanged, suggesting an independent and reciprocal effect of NO and PG in the cholinergic stimulation of pituitary-adrenocortical response. These results indicate that in the stimulatory action of muscarinic agonist, carbachol, NO is an inhibitory transmitter under basal and crowding stress conditions. This psychosocial stress does not functionally affect the NOS/NO systems. Prostaglandins are involved in the cholinergic muscarinic-induced stimulation of HPA response to a significant extent in non-stressed rats. PGE(2) may be involved in the carbachol-elicited HPA response under basal and stress conditions. Prostaglandins released in response to muscarinic stimulation did not evoke the hypothalamic CRH mediation. NO significantly impairs and PG stimulates the carbachol-induced HPA response in rats under basal and social stress conditions.
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PMID:The involvement of nitric oxide and prostaglandins in the cholinergic stimulation of hypothalamie-pituitary-adrenal response during crowding stress. 1703 98

There is an extensive evidence that corticotropin releasing factor (CRF) is hypersecreted in depression and anxiety, and blockade of CRF could have therapeutic benefit. We report preclinical data and the results of a clinical Phase I study with the novel nonpeptide CRF(1) antagonist NBI-34041/SB723620. Preclinical data conducted with different cell lines expressing human CRF receptors and in Wistar and Sprague-Dawley rats indicate that NBI-34041 is effective in reducing endocrine responses to pharmacological and behavioral challenge mediated by CRF(1) receptors. These specific properties and its well-documented safety profile enabled a clinical Phase I study with 24 healthy male subjects receiving NBI-34041 (10, 50, or 100 mg) or placebo for 14 days. Regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis was evaluated by intravenous stimulation with 100 microg of human CRF. Psychosocial stress response was investigated with the Trier Social Stress Test (TSST). Treatment with NBI-34041 did not impair diurnal adrenocorticotropic hormone (ACTH) and cortisol secretion or CRF evoked ACTH and cortisol responses but attenuated the neuroendocrine response to psychosocial stress. These results suggest that NBI-34041 is safe and does not impair basal regulation of the HPA system but improves resistance against psychosocial stress. NBI-34041 demonstrates that inhibition of the CRF system is a promising target for drug development against depression and anxiety disorders.
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PMID:High-affinity CRF1 receptor antagonist NBI-34041: preclinical and clinical data suggest safety and efficacy in attenuating elevated stress response. 1728 23


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