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)

We encountered a case with long-term remission of Cushing's disease due to pituitary apoplexy. The apoplexy of pituitary adenoma secreting adrenocorticotropin hormone was diagnosed by successive and timely magnetic resonance imaging when the symptoms of the patient were not yet severe and anterior pituitary dysfunction was only a transient reduction of growth hormone secretion. Seven years after the first episode of pituitary apoplexy, hypercorticism recurred, and pituitary magnetic resonance imaging showed a regrowth of the pituitary adenoma. A spontaneous remission of Cushing's disease without significant visual, neurologic or hormonal defects seems to be a much more common phenomenon than has been previously suggested. Cases with relapse after spontaneous remission of Cushing's disease are rare and the duration of remission in previous reports was within 5 years. We observed such a patient with a 7 year-remission caused by pituitary apoplexy. We consider that a careful long-term follow-up is required for patients with Cushing's disease whose remission was due to pituitary apoplexy.
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PMID:Recurrence of Cushing's disease after long-term remission due to pituitary apoplexy. 1122 56

Following stroke, an intracerebral inflammatory response develops that may contribute to postischemic central nervous system injury. This study's objective was to determine whether the anti-inflammatory neuropeptide alpha-melanocyte stimulating hormone (MSH) can suppress postischemic activation of intracerebral tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) gene expression. Ipsilateral TNF-alpha levels were increased in cerebrocortical territory of the middle cerebral artery (MCA) following transient unilateral MCA occlusion (MCAO) and reperfusion in mice, and systemic alpha-MSH treatment (0.5 mg/kg i.p.) suppressed this increase. Systemic alpha-MSH treatment also inhibited the marked increases in cortical TNF-alpha and IL-1beta mRNA levels following MCAO, and reduced the intracerebral TNF-alpha protein levels seen after transient global ischemia. We conclude that alpha-MSH treatment suppresses intracerebral proinflammatory cytokine gene expression following transient cerebral ischemia, suggesting that systemically administered melanocortins may exert neuroprotective effects in cerebral ischemia.
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PMID:Alpha-melanocyte stimulating hormone suppresses intracerebral tumor necrosis factor-alpha and interleukin-1beta gene expression following transient cerebral ischemia in mice. 1245 26

Housing rats in an enriched environment improves functional outcome after ischemic stroke, this may reflect neuronal plasticity in brain regions outside the lesion. Which components of the enriched environment that are of greatest importance for recovery after brain ischemia is uncertain. We have previously found that enriched environment and social interaction alone both improve functional recovery after focal cerebral ischemia, compared with isolated housing with voluntary wheel-running. In this study, the aim was to separate components of the enriched environment and investigate the effects on some potential mediators of improved functional recovery; such as the inducible transcription factors nerve growth factor-induced gene A (NGFI-A) and NGFI-B, and the glucocorticoid and serotonin systems. After permanent middle cerebral artery occlusion, rats were divided into four groups: individually housed with no equipment (deprived group), individually housed with free access to a running wheel (running group), housed together in a large cage with no equipment (social group) or in a large cage furnished with exchangeable bars, chains and other objects (enriched group). mRNA expression of inducible transcription factors, serotonin and glucocorticoid receptors was determined with in situ hybridisation 1 month after cerebral ischemia. Rats housed in enriched or social environments showed significantly higher mRNA expression of NGFI-A and NGFI-B in cortical regions outside the lesion and in the CA1 (cornu ammonis region of the hippocampus), compared with isolated rats with or without a running wheel. NGFI-A and NGFI-B mRNA expression in cortex and in CA1 was significantly correlated to functional outcome. 5-Hydroxytryptamine receptor 1A (5-HT(1A)) mRNA expression and binding, as well as 5-HT(2A) receptor mRNA expression were decreased in the hippocampus (CA4 region) of the running wheel rats. Mineralocorticoid receptor gene expression was increased in the dentate gyrus amongst wheel-running rats. No group differences were found in plasma corticosterone levels or mRNA levels of glucocorticoid receptor, corticotropin-releasing hormone, 5-HT(2C) or c-fos. In conclusion, we have found that social interaction is a major component of the enriched environment regarding the effects on NGFI-A and NGFI-B expression. These transcription factors may be important mediators of improved functional recovery after brain infarctions, induced by environmental enrichment.
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PMID:Effects of postischemic environment on transcription factor and serotonin receptor expression after permanent focal cortical ischemia in rats. 1280 85

Corticotropin releasing hormone (CRH) and its family of related peptides are involved in regulating physiologic responses to multiple stressors, including stroke. Although CRH has been implicated in the exacerbation of injury after stroke, the mechanism remains unclear. After ischemia, both excitotoxic damage and inflammation contribute to the pathology of stroke. CRH is known to potentiate excitotoxic damage in the brain and has been shown to modulate inflammatory responses in the periphery. Here the present authors examine the relative contribution of the two known CRH receptors, CRH-R1 and CRH-R2, to ischemic injury using CRH receptor knockout mice. These results implicate CRH-R1 as the primary mediator of ischemic injury in this mouse model of stroke. In addition, the authors examine a potential role for CRH in inflammatory injury after stroke by identifying functional CRH receptors on astrocytes and microglia, which are cells that are known to be involved in brain inflammation. By single cell PCR, the authors show that microglia and astrocytes express mRNA for both CRH-R1 and CRH-R2. However, CRH-R1 is the primary mediator of cAMP accumulation in response to CRH peptides in these cells. The authors suggest that astrocytes and microglia are cellular targets of CRH, which could serve as a link between CRH and inflammatory responses in ischemic injury via CRH-R1.
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PMID:Reduced cerebral injury in CRH-R1 deficient mice after focal ischemia: a potential link to microglia and atrocytes that express CRH-R1. 1452 25

Adrenocorticotroph cell pituitary adenomas immunoreactive for adrenocorticotropic hormone (ACTH) but unassociated with preoperative signs of hypercortisolism constitute between 6% and 43% of all ACTH adenomas. Few large series have been published. At our referral center for pituitary diseases, we have encountered 12 patients with silent ACTH adenomas, none of whom exhibited definite clinical features of hypercortisolism preoperatively. Two patients presented with apoplexy, and in 2 patients preoperative neuroimaging studies mimicked craniopharyngioma. Pathological examination revealed 8 adenomas with variably basophilic cytoplasm (type I, including 1 each with coarse basophilic granules and Crooke's hyaline change) and 4 with predominantly chromophobic cytoplasm (type II). Diffuse versus patchy (30% to 50% of cells) immunostaining best distinguished these 2 types; calcitonin staining was focal or negative in both. Two patients had unexpected postoperative courses consistent with acute cortisol insufficiency; 1 patient suffered from a severe flu-like illness, and the other had dizziness and was found to have a serum cortisol level of < 1.0 microg/dL. Both patients improved after cortisol replacement followed by a slow taper. Another patient developed 2 separate pituitary adenomas, a silent ACTH adenoma followed by a pure prolactinoma resected months later. Clonality studies demonstrated that the 2 tumors had arisen from different clonal populations. These cases offer additional insights into clinical, neuroimaging, histological, and biological features of silent ACTH adenomas. Because 2 of these patients seemed to require postoperative cortisol supplementation that otherwise would not have been given, clinicians should be notified about ACTH immunostaining in adenomas from patients without preoperative diagnoses of Cushing's disease, to optimize postoperative care.
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PMID:Silent corticotroph adenomas: further clinical and pathological observations. 1534 17

Heat stroke is characterized by hyperthermia, arterial hypotension, decreased baroreflex sensitivity, and increased serum levels of beta-endorphin. Whereas naltrexone may have therapeutic potential in heat stroke, the underlying mechanism remains unclear. We tested the hypothesis that naltrexone may attenuate heat stroke by reducing hyperthermia, hypotension, decreased baroreceptor sensitivity, and/or increased serum levels of beta-endorphin. Heat stroke was induced by exposing the anesthetized adult Sprague-Dawley rats in an incubator at 43 degrees C. The moment in which the mean arterial pressure dropped irreversibly from the peak level was taken as the onset of heat stroke. Control rats were exposed to 24 degrees C. Mean arterial pressure, baroreceptor sensitivity, and maximal reflex bradycardia, after the onset of heat stroke, were all significantly lower than in control rats. However, rectal temperature and serum levels of beta-endorphin were all greater after the onset of heat stroke. Intravenous delivery of naltrexone (10 mg/kg) 20 min before the initiation of heat stress, but not immediately at the onset of heat stroke, significantly attenuated the above-mentioned reactions. Accordingly, naltrexone improved survival during heat stroke. These results suggest that naltrexone protects against hypotension and decrement of both baroreceptor sensitivity and maximal reflex bradycardia during heat stroke by reducing both hyperthermia and increment of serum beta-endorphin and thus improves survival.
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PMID:Naltrexone protects against hypotension, hyperthermia, and beta-endorphin overproduction during heatstroke in the rat. 1582 38

G protein-coupled receptors (GPCRs) play pivotal roles in regulating the function and plasticity of neuronal circuits in the nervous system. Among the myriad of GPCRs expressed in neural cells, class II GPCRs which couples predominantly to the Gs-adenylate cyclase-cAMP signaling pathway, have recently received considerable attention for their involvement in regulating neuronal survival. Neuropeptides that activate class II GPCRs include secretin, glucagon-like peptides (GLP-1 and GLP-2), growth hormone-releasing hormone (GHRH), pituitary adenylate cyclase activating peptide (PACAP), corticotropin-releasing hormone (CRH), vasoactive intestinal peptide (VIP), parathyroid hormone (PTH), and calcitonin-related peptides. Studies of patients and animal and cell culture models, have revealed possible roles for class II GPCRs signaling in the pathogenesis of several prominent neurodegenerative conditions including stroke, Alzheimer's, Parkinson's, and Huntington's diseases. Many of the peptides that activate class II GPCRs promote neuron survival by increasing the resistance of the cells to oxidative, metabolic, and excitotoxic injury. A better understanding of the cellular and molecular mechanisms by which class II GPCRs signaling modulates neuronal survival and plasticity will likely lead to novel therapeutic interventions for neurodegenerative disorders.
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PMID:Class II G protein-coupled receptors and their ligands in neuronal function and protection. 1605 36

Ischemic stroke is one of the main causes of death and disability. We investigated whether melanocortin peptides, which have protective effects in severe hypoxic conditions, also produce neuroprotection in a gerbil model of ischemic stroke. A 10-min period of global cerebral ischemia, induced by occluding both common carotid arteries, caused impairment in spatial learning and memory that was associated with activation of inflammatory and apoptotic pathways, including severe DNA damage and delayed neuronal death, in the hippocampus. Treatment with nanomolar doses of the melanocortin analog [Nle4, D-Phe7] alpha-MSH [which activates the melanocortin receptor subtypes (MC) mainly expressed in central nervous system, namely MC3 and MC4] modulated the inflammatory and apoptotic cascades and reduced hippocampus injuries even when delayed up to 9 h after ischemia, with consequent dose-dependent improvement in subsequent functional recovery. The selective MC3 receptor agonist gamma2-MSH had no protective effects. Pharmacological blockade of MC4 receptors prevented the neuroprotective effects of [Nle4, D-Phe7] alpha-MSH and worsened some ischemia outcomes. Together, our findings suggest that MC4 receptor-stimulating melanocortins might provide potential to develop a class of drugs with a broad treatment window for a novel approach to neuroprotection in ischemic stroke.
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PMID:Both early and delayed treatment with melanocortin 4 receptor-stimulating melanocortins produces neuroprotection in cerebral ischemia. 1648 82

The aim of the study was to investigate the effects of alpha-melanocyte-stimulating hormone (alpha-MSH), a tridecapeptide derived from proopiomelanocortin (POMC), on the neurodegeneration following global cerebral ischemia and reperfusion in the rat. The biological activities of alpha-MSH include inhibition of inflammatory responses and anti-pyretic effects. Male Sprague-Dawley rats were subjected to four-vessel occlusion (4-VO) global cerebral ischemia followed by reperfusion, and treated with alpha-MSH (intraperitoneally, i.p.) at 30 min, and 24, 48, 72 and 96 h post-ischemia. Stereological quantification of the pyramidal cells in the CA1 area of the hippocampus showed that the number of viable neurons in ischemic rats was 96,945+/-18,610 (means+/-SD) as compared to 183,156+/-49,935 in sham-operated rats (P<0.05). The number of viable neurons after treatment of ischemic rats with alpha-MSH was 162,829+/-34,757, i.e. significantly different from the number of viable neurons in ischemic rats injected with saline (P<0.01). Astrocyte proliferation due to the ischemic insult was markedly reduced by the treatment with alpha-MSH, and the loss in body weight was reduced by alpha-MSH. In conclusion, post-ischemic administration of alpha-MSH was found to provide neuroprotection in the CA1 pyramidal cell layer in the hippocampus, concomitant with a reduction in glial activation, indicating that alpha-MSH or mimetics thereof may have a potential in the treatment of stroke or other neurodegenerative diseases. Further studies will be required to define the post-ischemic time window for administration of alpha-MSH.
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PMID:alpha-Melanocyte-stimulating hormone is neuroprotective in rat global cerebral ischemia. 1641 16

Melanocortin peptides have been shown to produce neuroprotection in experimental ischemic stroke. The aim of the present investigation was to identify the therapeutic treatment window of melanocortins, and to determine whether these neuropeptides chronically protect against damage consequent to brain ischemia. A 10-min period of global cerebral ischemia in gerbils, induced by occluding both common carotid arteries, caused impairment in spatial learning and memory (Morris test: four sessions from 4 to 67 days after the ischemic episode), associated with neuronal death in the hippocampus. Treatment with a nanomolar dose (340 microg/kg i.p., every 12 h for 11 days) of the melanocortin analog [Nle(4), D-Phe(7)]alpha-melanocyte-stimulating hormone (NDP-alpha-MSH), starting 3-18 h after the ischemic episode, reduced hippocampal damage with improvement in subsequent functional recovery. The protective effect was long-lasting (67 days, at least) with all schedules of NDP-alpha-MSH treatment; however, in the latest treated (18 h) gerbils, some spatial memory deficits were detected. Pharmacological blockade of melanocortin MC(4) receptors prevented the protective effects of NDP-alpha-MSH. Our findings indicate that, in conditions of brain ischemia, melanocortins can provide strong and long-lasting protection with a broad therapeutic treatment window, and with involvement of melanocortin MC(4) receptors, 18 h being the approximately time-limit for stroke late treatment to be effective.
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PMID:Broad therapeutic treatment window of [Nle(4), D-Phe(7)]alpha-melanocyte-stimulating hormone for long-lasting protection against ischemic stroke, in Mongolian gerbils. 1664


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