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)

Studies examining the function of the hypothalamic-pituitary-adrenal (HPA) axis in anorexia nervosa are reviewed. A principal finding is that of hypercortisolism, associated with increased central corticotropin-releasing hormone levels and normal circulating levels of adrenocorticotropic hormone. Similarities between neuroendocrine findings in anorexia nervosa and in affective disorder are reviewed. The contribution of circadian rhythm disturbances and malnutrition to observed HPA axis abnormalities in anorexia nervosa is also considered. Directions for future research are discussed.
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PMID:The hypothalamic-pituitary-adrenal axis in anorexia nervosa. 873 17

Although the involvement of both endogenous opioid and serotonergic systems in modulation of pain and emotion was suggested, the neurochemical interaction between these systems in the brain has not previously been studied directly. Herein, the effects of the local application of serotonin (5-HT) and fluoxetine (a 5-HT reuptake inhibitor) on extracellular levels of beta-endorphin in the arcuate nucleus and nucleus accumbens were assessed in freely moving rats using in vivo microdialysis. The mean basal concentrations of beta-endorphin in dialysates obtained from the arcuate nucleus and nucleus accumbens were 259.9 and 143.3 pM, respectively. Specific lesion of the serotonergic system by 5,7-dihydroxytryptamine (5,7-DHT) caused a significant decrease in these dialysate beta-endorphin levels. When 5-HT (0.25-5 microM) was added to the perfusion solution, the levels of beta-endorphin in the dialysate from the arcuate nucleus increased (186-296% of baseline), in a concentration-dependent manner. In the nucleus accumbens, 0.5 and 2 microM 5-HT in the perfusion fluid did not affect the levels of beta-endorphin in the dialysate, whereas 5 and 10 microM 5-HT caused an increase of approximately 190% of baseline. When fluoxetine (250 microM) was present in the perfusing solution, the levels of beta-endorphin in the dialysates from the arcuate nucleus and nucleus accumbens increased two- to threefold. This effect was not obtained in the 5,7-DHT-lesioned rats. Thus, 5-HT, either endogenously or exogenously delivered, appears to facilitate the release of beta-endorphin in the arcuate nucleus and nucleus accumbens. This indication of an interaction between serotonergic and endorphinic systems may be relevant for assessing pain and mood disorder circuits and the mode of action of antidepressant drugs.
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PMID:Serotonin-mediated increases in the extracellular levels of beta-endorphin in the arcuate nucleus and nucleus accumbens: a microdialysis study. 1058 20

The present article summarizes the main results of the cross-sectional part of the 'Munich Vulnerability Study' in which healthy first-degree relatives of patients with an affective disorder were investigated by assessing their neuroendocrine, polysomnographic and psychometric status. As patients with an acute episode of a major depression, the group of the healthy relatives exhibited signs of a hyperactive hypothalamic-pituitary-adrenocortical system verified by the combined dexamethasone corticotropin-releasing hormone (DEX/CRH) test, as well as a slow wave sleep deficit in the first sleep cycle and an increased amount of rapid eye movements during REM sleep. The psychometric profile of the healthy relatives was characterised by elevated scores on the scales measuring 'Rigidity' and 'Autonomic Lability'. On a single-case level, 32% of the healthy first-degree relatives of patients with an affective disorder exhibited 'depression-like' features or conspicuous findings in at least two of the three (i.e. neuroendocrine, polysomnographic, psychometric) areas assessed. Whether the relatives with the neurobiological and psychometric abnormalities we identified have a higher risk for developing an affective disorder than those without has to be answered by the still ongoing prospective part of the study.
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PMID:Neuroendocrine, polysomnographic and psychometric observations in healthy subjects at high familial risk for affective disorders: the current state of the 'Munich vulnerability study'. 1117 71

Several lines of evidence suggest a dysregulation of the adrenocortical (HPA) system with hypersecretion of CRH is associated with suicidal behavior. However, controversial results have emerged from the determination of corticotropin-releasing hormone (CRH) concentrations in the lumbar cerebrospinal fluid (CSF) of suicide attempters probably due to methodological differences. We simultaneously measured CRH concentrations in the CSF and in the plasma of 41 psychiatric in-patients with different diagnoses (affective disorder, schizophrenia, personality disorders, adjustment disorder, substance abuse) and eight neurological control subjects. We also measured plasma cortisol concentrations because data from animal experiments suggest that cortisol may influence CSF CRH concentrations. The major finding was that patients who attempted suicide prior to admission had significantly lower CSF CRH concentrations than psychiatric patients without suicidal behavior. CRH concentrations were significantly higher in the CSF than in plasma in both, psychiatric patients and neurological control subjects. There was no significant difference between suicide attempters and patients with acute suicidal ideations. The latter group showed a trend towards lower CSF CRH concentrations compared with the neurological control subjects. Patients with affective disorder alone as well as patients with multiple diagnoses, but not schizophrenic patients, showed significantly lower CSF CRH concentrations than neurological control subjects. Plasma CRH and plasma cortisol concentrations did not differ among diagnostic groups or between suicide attempters vs. non-attempters. Further studies with more homogeneous samples, drug-free patients and with simultaneous assessment of various parameters of the HPA system are warranted.
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PMID:Decreased corticotropin-releasing hormone (CRH) concentrations in the cerebrospinal fluid of eucortisolemic suicide attempters. 1128 50

Profound alterations of the hypothalamic-pituitary-thyroid (HPT) and the hypothalamic-pituitary-adrenal (HPA) systems at the hypophyseal level have been described in affective disorder. To precisely characterize the basal alterations of both axes during sleep, we simultaneously investigated sleep EEG and the secretion of thyrotropin, ACTH and cortisol in nine drug-free male patients with depression in comparison to 10 healthy age and sex matched controls. In depressed patients the nearly diametrical nocturnal secretion of thyrotropin and ACTH was disturbed by significantly blunted thyrotropin values (TSH AUC 51.96+/-5.68 vs. 87.23+/-13.63, P<0.05) and elevated ACTH values (ACTH AUC 1804+/-161 vs. 1538+/-130, P<0.05) compared to controls. Moreover, cross correlation analysis revealed a highly negative association of 0 lag between thyrotropin and ACTH and between thyrotropin and cortisol in the control sample, indicating a physiological nocturnal negative correlation of HPT and HPA system. In the patients sample these associations were weak and reached not statistical significance. Therefore, as a descriptive tool, the ratio TSH/ACTH revealed a significant group difference between controls and patients in the first half of the night (TSH/ACTH AUC 6.50+/-0.42 vs. 3.35+/-0.31, P<0.05). Sleep-EEG analysis showed a shortened REM latency, a decrease of stage 2 and an increase of awake time in the patients. Our data support the hypothesis that both hypophyseal hormones reflect a common dysregulation of both systems in depression probably due to impaired action of TRH-related corticotropin-release-inhibiting-factor (CRIF). The ratio TSH/ACTH might be a tool to characterize alterations of both the HPT and HPA axis in depression during the first half of the night.
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PMID:Nocturnal secretion of TSH and ACTH in male patients with depression and healthy controls. 1188 97

One of the most characteristic alterations in depression is a disturbed regulation of the hypothalamic-pituitary-adrenocortical (HPA) system. A function test combining the pre-treatment of 1.5 mg dexamethasone (DEX) with a challenge of 100 microg corticotropin-releasing hormone (CRH) reveals a pathological increase in the adrenocorticotropin and cortisol release in patients with major depression. These changes partially persist after successful treatment with remission and therefore, might represent trait or vulnerability markers. To further address this question, we were investigating the premorbid neuroendocrine profile of 74 healthy high-risk probands (HRPs) with a positive family history for affective disorders. The aim was to identify premorbid vulnerability factors. During the observation period, 19 HRPs developed an affective disorder. Their premorbid DEX/CRH test results were compared with 19 age- and sex matched controls. No significant differences could be observed between these two groups. Our results suggest that a dysregulated HPA system indicated by this function test can rather be regarded as a neurobiological scar developing during the course of affective disorders.
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PMID:The Munich vulnerability study on affective disorders: premorbid neuroendocrine profile of affected high-risk probands. 1550 20

Depression is characterized by hypothalamo-pituitary-adrenocortical (HPA) axis hyperactivity. In this major mood disorder, neurosteroids and neurotrophins, particularly brain-derived neurotrophic factor (BDNF), seem to be implicated and have some antidepressant effects. BDNF is highly involved in regulation of the HPA axis, whereas neurosteroids effects have never been clearly established. In this systematic in vivo study, we showed that the principal neuroactive steroids, namely dehydroepiandrosterone (DHEA), pregnenolone (PREG) and their sulfate esters (DHEA-S and PREG-S), along with allopregnanolone (ALLO), stimulated HPA axis activity, while also modulating central BDNF contents. In detail, DHEA, DHEA-S, PREG, PREG-S and ALLO induced corticotropin-releasing hormone (CRH) and/or arginine vasopressin (AVP) synthesis and release at the hypothalamic level, thus enhancing plasma adrenocorticotropin hormone (ACTH) and corticosterone (CORT) concentrations. This stimulation of the HPA axis occurred concomitantly with BDNF modifications at the hippocampus, amygdala and hypothalamus levels. We showed that these neurosteroids induced rapid effects, probably via neurotransmitter receptors and delayed effects perhaps after metabolization in other neuroactive steroids. We highlighted that they had peripheral effects directly at the adrenal level by inducing CORT release, certainly after estrogenic metabolization. In addition, we showed that, at the dose used, only DHEA, DHEA-S and PREG-S had antidepressant effects. In conclusion, these results highly suggest that part of the HPA axis and antidepressant effects of neuroactive steroids could be mediated by BDNF, particularly at the amygdala level. They also suggest that neurosteroids effects on central BDNF could partially explain the trophic properties of these molecules.
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PMID:Neuroactive steroids modulate HPA axis activity and cerebral brain-derived neurotrophic factor (BDNF) protein levels in adult male rats. 1792 60

Depression is a debilitating mood disorder that is among the top causes of disability worldwide. It can be characterized by a set of somatic, emotional, and behavioral symptoms, one of which is a high risk of suicide. This work presents a hypothesis that depression may be caused by the convergence of two factors: (A) A lifestyle that lacks certain physiological stressors that have been experienced by primates through millions of years of evolution, such as brief changes in body temperature (e.g. cold swim), and this lack of "thermal exercise" may cause inadequate functioning of the brain. (B) Genetic makeup that predisposes an individual to be affected by the above condition more seriously than other people. To test the hypothesis, an approach to treating depression is proposed that consists of adapted cold showers (20 degrees C, 2-3 min, preceded by a 5-min gradual adaptation to make the procedure less shocking) performed once or twice daily. The proposed duration of treatment is several weeks to several months. The following evidence appears to support the hypothesis: Exposure to cold is known to activate the sympathetic nervous system and increase the blood level of beta-endorphin and noradrenaline and to increase synaptic release of noradrenaline in the brain as well. Additionally, due to the high density of cold receptors in the skin, a cold shower is expected to send an overwhelming amount of electrical impulses from peripheral nerve endings to the brain, which could result in an anti-depressive effect. Practical testing by a statistically insignificant number of people, who did not have sufficient symptoms to be diagnosed with depression, showed that the cold hydrotherapy can relieve depressive symptoms rather effectively. The therapy was also found to have a significant analgesic effect and it does not appear to have noticeable side effects or cause dependence. In conclusion, wider and more rigorous studies would be needed to test the validity of the hypothesis.
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PMID:Adapted cold shower as a potential treatment for depression. 1799 52

Sodium butyrate (NaB), a histone deacetylase inhibitor, has been implicated in the antidepressant-like effects either injected as a single drug or in combination with selective serotonin reuptake inhibitor (SSRI), such as fluoxetine. Estrogen is also demonstrated to have antidepressant effect especially together with fluoxetine. We investigated whether NaB administered in combination with estradiol benzoate (EB) exerted antidepressant-like effect in forced swimming test (FST) in ovariectomized female rats. Furthermore, we detected the mRNA expressions of serotonin receptors and neuropeptides in hypothalamus, both of which participate in the mood disorder. Ovariectomized female SD rats were treated with vehicle, NaB, EB or NaB combined with EB for 7 days and then subjected to FST. The expressions of serotonin receptors (5-hydroxytryptamine receptor), corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) mRNA in the hypothalamus were detected by real time PCR. We found that co-treated with NaB and EB resulted in a significant decrease in immobility behavior in FST, a measure for depression-like behavioral. 5-HT(1A) antagonist, WAY 100635, significantly block the antidepressant-like effects induced by NaB plus EB. The mRNA expression of the serotonin-1A [5-hydroxytryptamine 1A (5-HT(1A))] receptor was increased in the co-treated group in hypothalamus, while there was no difference in the mRNA expression of 5-HT(2A) or 5-HT(2C). The mRNA expression of CRH or AVP was not significantly altered either. In conclusion, NaB may exert antidepressant-like effects in combination with EB in ovariectomized female rats through 5-HT(1A) receptor, via altering the expression of 5-HT(1A) in the hypothalamus.
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PMID:Antidepressant-like effects of sodium butyrate in combination with estrogen in rat forced swimming test: involvement of 5-HT(1A) receptors. 1881 16

Profound dysfunctions in several neuroendocrine systems have been described in patients suffering from affective disorders such as major depression. In order to elucidate the mechanisms underlying these functional alterations, animal models including mice genetically modified by either direct gene-targeting or by selective breeding approaches have been used exceedingly, revealing valuable insights into neuroendocrine pathways conserved between rodents and men. This review focuses on altered function and regulation of the hypothalamic-pituitary-adrenocortical axis, including its involvement in emotionality and stress responsiveness. In this context, the corticotropin-releasing hormone system and disturbances in glucocorticoid receptor signaling seem to be of central importance. However, changes in the expression and release patterns of vasopressin, dopamine and serotonin have also been shown to contribute to variation in emotionality, stress coping, cognitive functions and social behaviors. Affective disorders show a high degree of complexity, involving a multitude of molecular, neuroendocrine, and behavioral alterations as well as an intense gene-environment interaction, making it difficult to dissociate the primary causes from secondary consequences of the disease. Thus, interdisciplinary research, as applied in the emerging field of systems biology, involving adequate animal models and combined methodologies can significantly contribute to our understanding regarding the transmission of genetic predispositions into clinically relevant endophenotypes. It is only with deep insight into the mechanisms by which the stress hormone systems are regulated that novel treatment strategies and promising targets for therapeutic interventions can be developed in the future. Such in-depth understanding is ultimately essential to realizing our goal of predictive, preventive, and personalized medicine.
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PMID:Stress and affective disorders: animal models elucidating the molecular basis of neuroendocrine-behavior interactions. 2154 41


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