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)

In Xenopus laevis, corticotrophin-releasing factor (CRF) and urocortin 1 are present in the brain and they both are potent stimulators of alpha-melanophore stimulating hormone (MSH) secretion by melanotroph cells in the pituitary gland. Because both CRF and urocortin 1 bind with high affinity to CRF receptor type 1 (CRF1) in mammals and Xenopus laevis, one of the purposes of the present study was to identify the sites of action of CRF and urocortin 1 in the Xenopus brain and pituitary gland. Moreover, we raised the hypothesis that the external light intensity is a physiological condition controlling CRF1 expression in the pituitary melanotroph cells. By in situ hybridisation, the presence of CRF1 mRNA is demonstrated in the olfactory bulb, amygdala, nucleus accumbens, preoptic area, ventral habenular nuclei, ventromedial thalamic area, suprachiasmatic nucleus, ventral hypothalamic area, posterior tuberculum, tectum mesencephali and cerebellum. In the pituitary gland, CRF1 mRNA occurs in the intermediate and distal lobe. The optical density of the CRF1 mRNA hybridisation signal in the intermediate lobe of the pituitary gland is 59.4% stronger in white-adapted animals than in black-adapted ones, supporting the hypothesis that the environmental light condition controls CRF1 mRNA expression in melanotroph cells of X. laevis, a mechanism likely to be responsible for CRF- and/or urocortin 1-stimulated secretion of alpha-MSH.
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PMID:Localisation and physiological regulation of corticotrophin-releasing factor receptor 1 mRNA in the Xenopus laevis brain and pituitary gland. 1696 98

The stress neuropeptides, corticotropin-releasing hormone (CRH) and urocortin (UCN), modulate the inflammatory response via the hypothalamus-pituitary-adrenal axis and locally, in a paracrine manner, act on mast and macrophage cells. Kupffer cells (KCs) are the resident macrophages of the liver. They represent the bulk of tissue macrophages in the body and they are the first to face invading noxious agents reaching the body via the portal circulation. The aim of the present report was to study the expression of the CRH system in rat KC and test its functionality. Our findings are as follows: (1) In highly purified KCs the transcripts of UCN, of its receptors CRHR1, CRHR2 and that of the pseudoreceptor CRH-binding protein (CRHBP) were present while that of CRH was not detectable. (2) Similarly, immunoreactive UCN, CRHR1, CRHR2 and CRHBP were easily detectable by immunohistochemistry and immunofluorescence in sections of whole rat liver (localized in KC) as well as in purified KC while CRH was again not detectable. (3) Exposure of purified KC to CRH or UCN suppressed lipopolysaccharide-induced tumor necrosis factor alpha production, an effect completely prevented by the CRHR1 and CRHR2 receptor antagonist astressin. Our data demonstrate the presence of UCN and its receptors in rat KC, the absence of CRH, and the functionality of these receptors. We propose that a UCN-based system may affect local inflammatory phenomena in the liver acting in a paracrine manner.
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PMID:Neuropeptide urocortin and its receptors are expressed in rat Kupffer cells. 1709 Sep 73

Corticotropin-releasing factor (CRF) is considered to be a main adrenocorticotropin-releasing factor in vertebrates. In non-mammalian species, CRF and related peptides cause the release of thyroid-stimulating hormone (TSH) from the anterior pituitary. The actions of CRF peptides are mediated by two G protein coupled receptors (CRF1 and CRF2) that have different ligand specificities. Using ligands that bind preferentially or selectively to the CRF2 we tested the hypothesis that TSH release by the amphibian pituitary gland is mediated by the CRF2. Injection of frog CRF, urocortin 1 or the CRF2-specific ligand urocortin 3 all produced significant, acute increases (by 2 h) in plasma thyroxine concentration in prometamorphic tadpoles. Chronic injections of CRF peptides accelerated tadpole metamorphosis, and the peptides with the highest affinity for the CRF2 (urocortin 1 and sauvagine) had the greatest potency. Ligands selective for the CRF2 (frog urocortin 3, mouse urocortins 2 and 3) all accelerated tadpole metamorphosis. We then tested frog urocortins 1 and 3, mouse urocortin 2 and sauvagine for their TSH-releasing activity using dispersed frog anterior pituitary cells in culture. All of the peptides tested markedly enhanced the release of TSH. Secretagogue-induced TSH release was completely blocked by the general CRF receptor antagonist astressin or the CRF2-specific antagonist antisauvagine-30. Conversely, the type 1 CRF receptor-specific antagonist antalarmin had no effect on TSH secretion. Our results support the hypothesis that CRF-induced TSH release by the amphibian pituitary gland is mediated by the CRF2.
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PMID:Involvement of the corticotropin-releasing factor (CRF) type 2 receptor in CRF-induced thyrotropin release by the amphibian pituitary gland. 1718 89

The preterm labor is a very important clinical problem, both in the diagnostic, prophylactic and therapeutic aspect. It is the leading cause of prenatal morbidity and mortality. Despite of numerous studies and hypotheses mechanisms responsible for human parturition and pre-term labor are unclear. More than 30 years ago it was documented, that placenta is the important source of hormones, cytokins and growth factors. Corticotropin-relasing hormone (CRH) and urocortin (new ligand of CRH receptor) secreted during pregnancy by placenta, chorion, amnion and uterine decidua probably plays important role in human parturition and preterm labor. Possibly the combined hormonal markers profile to predict preterm labor can be used in the future.
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PMID:[Placental corticotropin releasing-hormone and urocortin--possible role in mechanism of preterm labor]. 1720 87

Corticotropin-releasing hormone (CRH) is a major mediator of stress response in the brain-gut axis. Irritable bowel syndrome (IBS) is presumed to be a disorder of the brain-gut link associated with exaggerated response to stress. We first showed that peripheral administration of CRH aggravated visceral sensorimotor function as well as adrenocorticotropic hormone (ACTH) response in IBS patients. We then administered alpha-helical CRH (alphahCRH), a non-selective CRH receptor antagonist among IBS patients. Electrical stimulation of the rectum induced significantly higher motility indices of the colon in IBS patients than in the controls. This response was significantly suppressed in IBS patients but not in the controls after administration of alphahCRH. Administration of alphahCRH induced a significant increase in the barostat bag volume of the controls but not in that of IBS patients. alphahCRH significantly reduced the ordinate scale of abdominal pain and anxiety evoked by electrical stimulation in IBS patients. Plasma ACTH and serum cortisol were generally not suppressed by alphahCRH. Last, administration of CRH1-receptor (CRH-R1) specific antagonist blocked colorectal distention-induced sensitization of the visceral perception in rats. Moreover, pretreatment with CRH-R1 antagonist blocked colorectal distention-induced anxiety, which was measured with elevated plus-maze, in rats. Evidence supporting the concept that peripheral CRH and CRH-R1 play important roles in brain-gut sensitization is increasing. Several studies have identified immunoreactive CRH and urocortin as well as CRH-R1 and CRH-R2 mRNAs in human colonic mucosa. In addition, reverse transcription-polymerase chain reaction has revealed the expression of CRH-R1 mRNA in both the myenteric and submucosal plexus in the guinea pig. Application of CRH has been shown to evoke depolarizing responses associated with elevated excitability in both myenteric and submucosal neurons. On the other hand, peripheral injection of CRH has been reported to induce discrete effects on colonic secretory and motor function, and permeability. There are functional differences between CRH-R1 and CRH-R2. For instance, activation of CRH-R1 causes a proinflammatory response, whereas stimulation of CRH-R2 provokes anti-inflammatory changes. In addition, there is evidence of the contrasting roles of CRH-R1 and CRH-R2 in visceral nociception. While CRH-R1 is involved in the pro-nociceptive effects of visceral pain, CRH-R2 mediates an anti-nociceptive response. These findings suggest the major role of CRH in stress-related pathophysiology of IBS and possibly in inflammation of the intestinal mucosa.
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PMID:Role of corticotropin-releasing hormone in irritable bowel syndrome and intestinal inflammation. 1723 26

There is increasing evidence that the sebaceous gland expresses receptors for several neuropeptides and is involved in responses to stress. Among them, corticotropin-releasing hormone (CRH) was currently found to be produced also in the skin. In this study, the distribution of CRH, CRH receptors 1 and 2 (CRH-R1 and CRH-R2), and CRH binding protein (CRH-BP) in cultured human (SZ95) sebocytes was further characterized. Moreover, the effects of CRH and CRH-like peptides on proliferation and inflammatory signaling of CRH receptor-expressing SZ95 sebocytes IN VITRO were investigated. Urocortin (Uct), urotensin and sauvagine are recently described members of the family of structurally related CRH-like peptides, whereas Uct shares a 45% homology with CRH. CRH and Uct inhibited SZ95 sebocyte proliferation with CRH also stimulating interleukin-6 (IL-6) and interleukin-8 (IL-8) release from SZ95 sebocytes. However, CRH had no effect on interleukin-1alpha and interleukin-1beta production in these cells. alpha-Helical-CRF, a CRH antagonistic peptide, annulled the CRH effect on SZ95 sebocyte proliferation and interleukin secretion, while the non-peptidic CRH-R1 selective antagonist antalarmin inhibited the increased production of neutral lipids caused by CRH. In conclusion, CRH, and to a lesser extent Uct, may be involved in signaling of stress pathophysiology in the skin. However, further investigations into the downstream effects of CRH and Uct are required to elucidate the mechanism by which these neuropeptides could establish a stress-related pathophysiological condition in the skin.
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PMID:Corticotropin-releasing hormone skin signaling is receptor-mediated and is predominant in the sebaceous glands. 1732 13

Urocortin, a potent peptide inhibitor of feeding behavior, can enter the brain from blood by leptin-facilitated permeation across the blood-brain barrier. Here, we show in cultured RBE4 cerebral microvessel endothelial cells that urocortin endocytosis is increased by leptin in a time- and dose-dependent manner. Fluorescently labeled urocortin (Alexa488-urocortin) shows vesicular trafficking localized in early endosomes at 1 min and the Golgi complex at 20 min. The endocytosis at 20 min was increased by 10 microg/mL, but not 2 microg/mL, of leptin. The facilitating effect of leptin at the dose of 10 microg/mL was seen at 20 and 30 min but not at 10 min. This increase could be abolished by excess unlabeled urocortin in radio-tracer uptake studies, indicating selective rather than nonsaturable entry. The specificity of the effect was further supported by the lack of changes in gamma-glutamyl transpeptidase activity and endothelial nitric oxide synthase upon stimulation by high doses of leptin and urocortin. Leptin did not affect the level of expression of the urocortin corticotropin-releasing hormone receptor (CRHR) after 30 min of treatment but appeared to slow the turnover of CRHRs induced by urocortin. In MDCK cells overexpressing CRHR2, leptin facilitated urocortin uptake, whereas ObRa coexpression did not exert an additional effect. Thus, urocortin endocytosis is a saturable process leading to vesicular intracellular transport that can be enhanced by cell-surface leptin.
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PMID:Urocortin trafficking in cerebral microvessel endothelial cells. 1747 91

In an attempt to clarify the role of the type 2 corticotropin-releasing hormone (CRH) receptor (CRHR-2) in the brain in activation of the hypothalamic-pituitary-adrenocortical axis, we conducted experiments using male Wistar rats. First, an injection of urocortin-2 (7.5 microg) into the lateral ventricle resulted in transient increases in CRH heteronuclear RNA (hnRNA) in parvocellular paraventricular nucleus (PVN) and in plasma adrenocorticotropic hormone (ACTH), whereas sustained increases in arginine vasopressin (AVP) hnRNA and c-fos mRNA in the parvocellular PVN were observed as compared with vehicle treatment. Pretreatment with the selective CRHR-2 antagonist antisauvagine-30 (20 microg) into the lateral ventricle 15 min prior to agonist injection attenuated the stimulatory effects of urocortin-2 on the above-mentioned hypothalamic-pituitary-adrenal axis variables. These effects were similar or rather more potent than those induced by pretreatment with 50 microg of alpha-helical CRH. Second, we found longer-lasting increases in CRH and AVP hnRNA and c-fos mRNA in parvocellular PVN and in plasma ACTH following central administration of urocortin-3 (7.5 microg) than following urocortin-2. Pretreatment with antisauvagine-30 antagonized the effects of urocortin-3 on the above-mentioned variables. Finally, central administration of antisauvagine-30 as well as alpha-helical CRH profoundly attenuated restraint-stress-induced increases in AVP hnRNA. However, alpha-helical CRH, but not antisauvagine-30, attenuated restraint-stress-induced increases in CRH hnRNA in the PVN. Both antagonists transiently attenuated stress responses of c-fos mRNA in PVN and plasma ACTH. These results indicate that there is a CRHR-2-mediated mechanism in the brain that stimulates CRH- and AVP-producing neurons in the PVN which results in the promotion of plasma ACTH secretion.
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PMID:Central type 2 corticotropin-releasing hormone receptor mediates hypothalamic-pituitary-adrenocortical axis activation in the rat. 1755 Dec 62

The purpose of this study was to compare the effects of an acute stressor (restraint) versus a chronic stressor (social isolation) on the expression of mRNAs for corticotropin-releasing hormone receptor type 2 (CRH-R2) and urocortin 1 (Ucn 1) and urocortin 2 (Ucn 2) in the cardiovascular system of socially monogamous prairie voles of both sexes. Acute restraint for 1 h was followed by a marked increase in plasma corticosterone, and when the animals were re-paired for 1 day, the increment of corticosterone was normalized. However, following chronic social isolation for 4 weeks, plasma corticosterone did not differ significantly from the levels measured in animals living in pairs. Restraint or isolation significantly decreased CRH-R2 mRNA in ventricle, atria, and aorta; however, when these animals were re-paired for 1 day, the modulation of CRH-R2 mRNA was normalized in restraint but not in isolated animals. Restraint stress increased the Ucn 1 mRNA expression in the heart of female and male prairie voles, and when the animals were re-paired, the modulation of Ucn 1 mRNA expression was normalized. However, chronic isolation showed no effect on cardiac Ucn 1 mRNA expression. Although acute restraint stress produced no effect on the cardiac Ucn 2 mRNA expression, chronic isolation was followed by an increased heart Ucn 2 mRNA expression in both sexes. When the isolated animals were re-paired for 1 day, the cardiac Ucn 2 mRNA expression remained upregulated. The results of the present study reveal that acute restraint as well as social isolation can have significant consequences for the modulation of gene expression for the CRH-R2 and the urocortin peptides in cardiovascular tissue in female and male prairie voles.
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PMID:Modulation of corticotropin-releasing hormone type 2 receptor and urocortin 1 and urocortin 2 mRNA expression in the cardiovascular system of prairie voles following acute or chronic stress. 1755 Dec 67

Human reproduction is remarkably inefficient, with more than half of spontaneous conceptions failing to complete the first trimester. However, little is known on the molecular events that take place at the implantation site during abortion. Here, we examined the hypothesis that the expression of the proapoptotic Fas/FasL system at the implantation site is impaired in abortions. We found that, in contrast to normal pregnancy, abortive deciduas contain leukocytes that are positive for FasL and extravillous trophoblasts (EVTs), which show increased expression of Fas and increased rates of apoptosis. In addition, the neuropeptides, corticotropin-releasing hormone and urocortin, were elevated in placental material obtained from abortions. In vitro, these peptides induced the expression of FasL in decidual lymphocytes (DL) obtained from elective termination of pregnancy placentas and thus potentiated the cells' ability to induce Fas-mediated apoptosis in an EVT-based hybridoma cell line. Finally, DL from abortion sites effectively induced apoptosis of EVT without prior treatment. It is possible that these events may impede successful early placentation and thus contribute to the pathophysiology of human abortion.
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PMID:Abortion is associated with increased expression of FasL in decidual leukocytes and apoptosis of extravillous trophoblasts: a role for CRH and urocortin. 1770 18


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