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)

The process of aging is characterized by a disturbed neuroendocrine regulation, including a changed secretory activity of the hypothalamo-pituitary-adrenocortical (HPA) axis. In the present study adrenocorticotropin (ACTH) and cortisol secretion was monitored during nocturnal sleep (controlled by somnopolygraphy) in healthy aged men (N = 10, aged range 70-92 years, mean 78.2 years) and women (N = 10, age range 70-88 years, mean 78.6 years), and in young male controls (N = 16, age range 20-34 years, mean 24.9 years). Blood was drawn every 15 min. Most important, basal HPA secretory activity was enhanced distinctly in the elderly, as indicated by significantly elevated nadirs of plasma cortisol and ACTH concentrations occurring during early nocturnal sleep (p < 0.001, compared to young controls) and by elevated average levels of cortisol and ACTH between 23.00 and 03.00 h (p < 0.001). The first rise in nocturnal plasma cortisol began, on average, 67 min earlier than in young controls (p < 0.005). Changes of endocrine activity were associated with marked reductions of slow-wave sleep (SWS, p < 0.05) and rapid eye movement (REM) sleep in the elderly (p < 0.01), while time awake and in stage 1 sleep was increased. The REM sleep coincided with decreased HPA secretory activity, irrespective of age, indicating that the link between the ultradian sleep structure and the secretory HPA activity is maintained in the elderly.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Basal secretory activity of the hypothalamo-pituitary-adrenocortical axis is enhanced in healthy elderly. An assessment during undisturbed night-time sleep. 795 53

We recently described the expression of leukemia inhibitory factor (LIF) in human fetal and murine corticotrophs. LIF and the related cytokine oncostatin M induced basal, and corticotropin-releasing hormone (CRH) induced proopiomelanocortin (POMC) mRNA and ACTH secretion in AtT20 cells. LIF signaling and regulation of POMC gene transcription were therefore tested. Dexamethasone inhibited both basal- and LIF-induced ACTH secretion (P<0.05) and LIF induction of ACTH was also attenuated by immuneutralization of either the LIF receptor (35%, P<0.05) or the gp130 affinity converter (41%, P<0.05). These antisera also attenuated basal ACTH secretion in the absence of added ligand (P<0.05). To examine intrapituitary LIF signaling, phosphorylation of post-receptor substrates was measured. 1 nM LIF rapidly induced tyrosyl phosphorylation of STAT 1 and STAT 3 proteins, as well as tyrosyl phosphorylation of a 115-kD protein, coimmunoprecipitated with STAT 1. The transfected rat POMC promoter -706/+64, fused to the luciferase reporter gene, was induced by LIF, which exerted strong (18-fold) synergy with CRH. Deletion of the major CRH responsive region in POMC (-323/-166) abolished CRH induction of transcription and severely limited LIF synergy. Although 8 bromo cAMP or forskolin modestly enhanced POMC transcription (2.8-fold), LIF markedly potentiated (7.4-fold) these cAMP activators. These results demonstrate that corticotroph LIF action is receptor mediated and involves activation of STAT signaling pathways. LIF potently synergizes with both CRH and cAMP induction of POMC transcription. This novel intrapituitary signaling mechanism may mediate a neuroimmune pituitary interface.
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PMID:Leukemia inhibitory factor (LIF) stimulates proopiomelanocortin (POMC) expression in a corticotroph cell line. Role of STAT pathway. 862 68

The neuropeptides growth hormone-releasing hormone (GHRH) and corticotropin-releasing hormone (CRH) play a key role in sleep endocrine regulation. After pulsatile application of GHRH during the first few hours of the night in young normal controls SWS and GH increase, whereas cortisol is blunted. CRH however prompts inverse effects. The balance between these peptides is changed in favour of CRH physiologically during the second time of the night, during the acute episode of depression (due to overactivity of GRH) and in the elderly (due to reduced activity of CHRH). These changes explain the aberrances of sleep endocrine activity in these states, as shallow sleep, low GH and enhanced cortisol.
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PMID:[The role of neuropeptides in normal and disordered sleep regulation]. 901 57

A 1 h immobilization stress (IS) was imposed to rats at the beginning of the dark period, i.e., when the animals start to be active. The IS was accompanied by an intense polygraphic waking and followed, over 12 h of the dark period, by a significant rebound of slow-wave sleep (SWS, +17%) and paradoxical sleep (PS, +57%). In order to estimate the IS-related changes in the endogenous concentrations of corticotropin-like intermediate lobe peptide (CLIP, ACTH18-39) and related compounds, a specific radioimmunoassay (RIA) was used. Assays performed in cerebral biopsies taken from arcuate (AN) and raphe dorsalis (nRD) nuclei led to the obtention of 2 main immunoreactive peaks, corresponding to CLIP and its phosphorylated form Ph-CLIP. Just after end of the IS and within the nRD. Ph-CLIP immunoreactivity increased by about 95%. Four hours later, i.e., when PS rebound was maximal, a 37% increase in Ph-CLIP immunoreactivity was measured in the AN. These observations have never been described before. In the blood, at the end of the restraint, CLIP/ACTH1-39 total immunoreactivity was increased by 330%. It returned to baseline level 4 h later. Blood concentration of corticosterone was also increased by 56% at the end of the IS and was close to baseline level 4 h later. Data reported here indicate that the IS first triggers an increase in Ph-CLIP within the nRD. Since the nRD contains sleep permissive components, this increase might be determinant for the SWS and PS rebound induction. The changes observed in the blood as regards CLIP/ACTH1-39 total immunoreactivity and corticosterone concentration testify to the efficacy of the IS and are part of the conventional picture accompanying such a situation. Finally, the increase in Ph-CLIP, occurring in the AN 4 h after the end of the restraint, might be part of the restorative processes necessary to compensate the stress overshoot.
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PMID:Influence of a 1 h immobilization stress on sleep states and corticotropin-like intermediate lobe peptide (CLIP or ACTH18-39, Ph-ACTH18-39) brain contents in the rat. 909 68

A previous study demonstrated the efficacy of the corticotropin-releasing hormone (CRH) receptor antagonist, alpha-helical CRH (9-41), in blocking the paradoxical sleep increase induced by stress. In the present study, this peptide was used to evaluate the involvement of the stress component of the sleep deprivation, in the paradoxical sleep rebound. Rats were subjected for 10 h to the classical water-tank sleep-deprivation technique and were given, every 2 h throughout the sleep deprivation period, intracerebroventricular injections of either 100 microg/5 microl of alpha-helical CRH (9-41) or vehicle alone. Continuous recordings showed that antagonist treatment decreased the PS rebound, but not the SWS rebound, following sleep deprivation. These findings suggest that, in the water-tank sleep deprivation method, stress, acting via CRH activation, is the main factor inducing the paradoxical sleep rebound.
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PMID:Involvement of stress in the sleep rebound mechanism induced by sleep deprivation in the rat: use of alpha-helical CRH (9-41). 989 Feb 55

It is well known that the activation of the hypothalamic-pituitary-adrenal (HPA) axis can induce alterations in the sleep-wake pattern. Corticotropin-releasing factor (CRF), adrenocorticotropin, and corticosterone are involved in the activation of the axis and each one of them has shown an effect on wakefulness and sleep. Nevertheless, concerning corticosterone, the picture is still controversial. In the present study, we analyzed the effects of a low (LC, 0.2 mg), medium (MC, 2 mg), and high (HC, 4 mg) dose of corticosterone on the 24-h sleep cycle in rats. Results indicate that all doses produce an initial enhancement of wakefulness with a concomitant decrease of slow-wave sleep II (SWS II). This effect was observed within the first hour in all the doses but lasted until the third hour only after the higher doses. When plasma levels of corticosterone were analyzed by high-performance liquid chromatography (HPLC), the highest levels were observed during the first 3 h, which is coincident with an increase in the percentage of wakefulness. Nevertheless, when the overall percentage of the stages was analyzed, LC seemed to induce the opposite effect (decrease of wakefulness and increase of SWS II) than that induced by the two higher doses (increased wake time, decreased SWS II). Rapid eye movement (REM) sleep was not modified at any dose. These data indicate that corticosterone exerts an alerting effect that could be important in the initial stage of the stress response.
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PMID:Further definition of the effect of corticosterone on the sleep-wake pattern in the male rat. 1170 Dec 1

A bidirectional interaction exists between sleep electroencephalogram (EEG) and endocrine activity in various species including humans. Various hormones (peptides, steroids) were shown to participate in sleep regulation. A keyrole was shown for the reciprocal interaction between sleep-promoting growth hormone-releasing hormone (GHRH) and sleep-impairing corticotropin-releasing hormone (CRH). Changes in the GHRH:CRH ratio result in changes of sleep-endocrine activity. There is good evidence that the change of this ratio in favor of CRH contributes to aberrances of sleep during aging and depression. Besides of GHRH ghrelin and galanin promote SWS, whereas somatostatin is another sleep-impairing factor. NPY acts as a CRH antagonist and induces sleep onset. Prolactin enhances rapid eve-movement sleep (REMS) in rats. SWS is enhanced in patients with prolactinoma. Other studies on the influence of prolactin of human sleep are lacking. There is a controversy whether CRH promotes REMS. In humans vasocactive intestinal polypeptide (VIP) appears to play a role in the temporal organization of sleep, since after VIP administration the NREMS-REMS cycle decelerated. Several neuroactive steroids (pregnenolone, progesterone, allopregnanolone, dehydroepiandrosterone) exert specific effects on sleep EEG via GABAA receptors. Cortisol appears to enhance REMS. Finally gonadal hormones participate in sleep regulation. Estrogen replacement therapy and CRH-1 receptor antagonism in depression are beneficial clinical applications of the basic research presented here.
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PMID:Sleep and endocrine regulation. 1270 62