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)

Two analogs of human beta-endorphin (beta-EP) which contain cystine bridges, [Cys15-Cys26,Phe27,Gly31]-beta-EP (I) and [Cys16-Cys26,Phe27,Gly31]-beta-EP (II), were synthesized by the solid-phase method. Peptides I and II were shown to contain 2-2.5 times the opiate receptor binding activity of beta-endorphin. We also synthesized two analogs with reduced alkylated cysteine residues and these peptides, [Arg9,19,24,28,29 Cys(Cam)11,26,Phe27,Gly31] and [Arg9,19,24,28,29,Cys-(Cam)12,26,Phe27,Gly31], were shown to have approximately the same opiate receptor activity as beta-endorphin.
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PMID:Beta-endorphin. Synthesis and biological activity of analogs with disulfide bridges. 299 81

In the adult, corticotropin-releasing hormone (CRH) is the key mediator for the behavioural and neuroendocrine response to stress. It has also been hypothesized that, during postnatal development of the stress system, CRH controls the activity of the HPA axis and mediates the effects of early disturbances, e.g. 24 h of maternal deprivation. In the current study we investigated the function of specific brain corticotropin-releasing hormone receptor type 1 (CRHR1) subpopulations in the control of the HPA axis during postnatal development under basal conditions as well as after 24 h of maternal deprivation. We used two conditional CRHR1-deficient mouse lines which lack this receptor, either specifically in forebrain and limbic structures (Cam-CRHR1) or in all neurons (Nes-CRHR1). Basal circulating corticosterone was increased in Nes-CRHR1 mice compared to controls. Corticosterone response to maternal deprivation was significantly increased in both CRHR1-deficient lines. In the paraventricular nucleus, Cam-CRHR1 animals displayed enhanced CRH and decreased vasopressin expression levels. In contrast, gene expression in Nes-CRHR1 pups was strikingly similar to that in maternally deprived control pups. Furthermore, maternal deprivation resulted in an enhanced response of Cam-CRHR1 pups in the brain, while expression levels in Nes-CRHR1 mouse pups were mostly unchanged. Our results demonstrate that brainstem and/or hypothalamic CRHR1 contribute to the suppression of basal corticosterone secretion in the neonate, while limbic and/or forebrain CRHR1 dampen the activation of the neonatal HPA axis induced by maternal deprivation.
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PMID:Differential disinhibition of the neonatal hypothalamic- pituitary-adrenal axis in brain-specific CRH receptor 1-knockout mice. 1704 89

Impaired sleep and enhanced stress hormone secretion are the hallmarks of stress-related disorders, including major depression. The central neuropeptide, corticotropin-releasing hormone (CRH), is a key hormone that regulates humoral and behavioral adaptation to stress. Its prolonged hypersecretion is believed to play a key role in the development and course of depressive symptoms, and is associated with sleep impairment. To investigate the specific effects of central CRH overexpression on sleep, we used conditional mouse mutants that overexpress CRH in the entire central nervous system (CRH-COE-Nes) or only in the forebrain, including limbic structures (CRH-COE-Cam). Compared with wild-type or control mice during baseline, both homozygous CRH-COE-Nes and -Cam mice showed constantly increased rapid eye movement (REM) sleep, whereas slightly suppressed non-REM sleep was detected only in CRH-COE-Nes mice during the light period. In response to 6-h sleep deprivation, elevated levels of REM sleep also became evident in heterozygous CRH-COE-Nes and -Cam mice during recovery, which was reversed by treatment with a CRH receptor type 1 (CRHR1) antagonist in heterozygous and homozygous CRH-COE-Nes mice. The peripheral stress hormone levels were not elevated at baseline, and even after sleep deprivation they were indistinguishable across genotypes. As the stress axis was not altered, sleep changes, in particular enhanced REM sleep, occurring in these models are most likely induced by the forebrain CRH through the activation of CRHR1. CRH hypersecretion in the forebrain seems to drive REM sleep, supporting the notion that enhanced REM sleep may serve as biomarker for clinical conditions associated with enhanced CRH secretion.
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PMID:Conditional corticotropin-releasing hormone overexpression in the mouse forebrain enhances rapid eye movement sleep. 1945 48

Alterations in sleep patterns are often recognized as a premorbid symptom accompanied by affective disorders, particularly by major depression. However, the mechanism is rather complex, and differentiating its causalities from those of depression undergoes hardships. Indeed, depression is a complex disease. It has been clearly demonstrated that depressed patients display very characteristic changes in sleep architecture. Previous animal studies also demonstrated that several depression models, which had targeted elevated hypothalamic-pituitary-adrenocortical (HPA) axis, showed increased rapid eye movement (REM) sleep while insomniac sleep phenotype did not evidently appear. However, all stress hormones seem to be elevated in those models. Therefore, it has been difficult to determine which particular hormone in the HPA axis is primarily responsible for altered sleep in depression. In recent years, we have widely analyzed sleep characteristics of conditional transgenic mouse lines focusing on corticotropin-releasing hormone (CRH), the initial mediator of the HPA system, in which the levels of peripheral stress hormones are normal. Conditional CRH-overexpressing (COE) mice, especially those overexpress CRH limitedly within the forebrain including limbic structures (CRH-COE-Cam), dis- play enhanced REM sleep. Further, the higher occurrence of REM sleep in CRH-COE-Cam mice could be due to their hyper-cholinergic activity. REM sleep disinhibition observed in depressed patients similarly appears in animals which are genetically stress-vulnerable strain or chronically stressed, possibly due to enhanced action of limbic CRH. Indeed, REM sleep is a fragile vigilance state and closely connected with emotional control. Thus, depressive episodes may affect REM sleep earlier than nonREM sleep, and such altered REM sleep can be a state marker of depression.
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PMID:REM sleep alteration and depression. 2582 83