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)

Urocortin (Ucn) II and III, homologous peptides of Ucn that are specific ligands for corticotropin-releasing hormone (CRH) type 2 receptor (CRH-R2), have recently been identified. The present study was designed to elucidate the effects of Ucn II, which is predominantly expressed in rodent heart, on neonatal rat cardiac myocytes (MCs) and cardiac non-myocytes (NMCs). Ucn II increased the incorporation of [3H]-leucine into MCs, as well as the accumulation of cAMP and the secretion of atrial natriuretic peptide. However, no significant changes were demonstrated in NMCs or an MC/NMC co-culture system. The effects of Ucn II were attenuated by astressin2-B, a specific antagonist of CRH-R2, and/or H89, an inhibitor of protein kinase A (PKA). These results indicate that Ucn II may be another endogenous cardiovascular substance that acts via CRH-R2 and the cAMP-dependent PKA pathway.
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PMID:Effects of urocortin II on neonatal rat cardiac myocytes and non-myocytes. 1600 43

Urocortin (Ucn) 2 is a new member of the corticotrophin-releasing hormone (CRH) neuropeptide family that is expressed in the central nervous system and peripheral tissues. However, the expression levels of Ucn 2 in various tissues of the rat remains unclear. Thus, the aim of the present study was to characterise the expression of Ucn 2 in the various tissues of the rat. Reverse transcriptase-polymerase chain reaction analysis demonstrated that Ucn 2 mRNA is expressed in the hypothalamus, pituitary, adrenal, stomach, skin, ovary, uterus and skeletal muscle. Histologically, Ucn 2 mRNA and Ucn 2-like immunoreactivity (LI) were demonstrated in both the anterior and intermediate lobes of the pituitary, but not detected in the posterior lobe. Furthermore, all Ucn 2-positive cells in the anterior and intermediate lobes were also positive for beta-endorphin. Ucn 2 mRNA was detected in the adrenal cortex and medulla although Ucn 2-LI was only found in the adrenal medulla. High-performance liquid chromatography analysis of hypothalamic, pituitary, and adrenal extracts showed that the main Ucn 2-LI peak occurred at the same molecular size as that of synthetic Ucn 2. These results suggest that Ucn 2 is synthesised in various tissues, including the anterior and intermediate lobes of the pituitary and the adrenal.
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PMID:Distribution of urocortin 2 in various tissues of the rat. 1615 78

Corticotropin Releasing Hormone-Binding Protein (CRH-BP), a 37 kDa secreted glycoprotein, binds both CRH and urocortin with high affinity and is structurally unrelated to the CRH receptors. CRH-BP orthologues have been identified in multiple invertebrate and vertebrate species. It is strongly conserved throughout evolution, suggesting the maintenance of a structural conformation necessary for biological activity. CRH-BP is an important modulator of CRH activity; it inhibits CRH-induced ACTH secretion from pituitary corticotropes and may exert similar actions at central sites of CRH release. While the function of CRH-BP is thought to be primarily inhibitory, recent studies indicate that novel functional roles may exist in both the brain and pituitary. Regulation of CRH-BP expression by stress and metabolic factors are consistent with in vivo models of altered CRH-BP expression. Positive regulation of pituitary CRH-BP by reproductive hormones suggests that additional interactions between the stress and reproductive axes may exist. While recent research has focused on the evolutionary conservation, expanded sites of expression, regulation and in vivo function of CRH-BP, a more complete understanding of the central and peripheral functions of CRH-BP and its mechanisms of action will help elucidate its potential role in the etiology or treatment of disorders of CRH dysregulation.
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PMID:CRH-BP: the regulation and function of a phylogenetically conserved binding protein. 1636 64

Peptides of the corticotropin-releasing factor (CRF) family are expressed throughout the central nervous system (CNS) and in peripheral tissues where they play diverse roles in physiology, behavior, and development. Current data supports the existence of four paralogous genes in vertebrates that encode CRF, urocortin/urotensin 1, urocortin 2 or urocortin 3. Corticotropin-releasing factor is the major hypophysiotropin for adrenocorticotropin, and also functions as a thyrotropin-releasing factor in non-mammalian species. In the CNS, CRF peptides function as neurotransmitters/neuromodulators. Recent work shows that CRF peptides are also expressed at diverse sites outside of the CNS in mammals, and we found widespread expression of CRF and urocortins, CRF receptors and CRF binding protein (CRF-BP) genes in the frog Xenopus laevis. The functions of CRF peptides expressed in the periphery in non-mammalian species are largely unexplored. We recently found that CRF acts as a cytoprotective agent in the X. laevis tadpole tail, and that the CRF-BP can block CRF action and hasten tail muscle cell death. The expression of the CRF-BP is strongly upregulated in the tadpole tail at metamorphic climax where it may neutralize CRF bioactivity, thus promoting tail resorption. Corticotropin-releasing factor and urocortins are also known to be cytoprotective in mammalian cells. Thus, CRF peptides may play diverse roles in physiology and development, and these functions likely arose early in vertebrate evolution.
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PMID:Widespread tissue distribution and diverse functions of corticotropin-releasing factor and related peptides. 1641 23

The corticotropin-releasing hormone (CRH) system, consisting of CRH and the homologue neuropeptide urocortin together with their receptors CRH(1) and CRH(2) and a specific binding protein (CRH-BP), holds the main role in mediating the response to stressful stimuli. Besides their expression in the brain, CRH peptides and receptors have been found in multiple peripheral sites. Here we investigate the expression of CRH, urocortin, CRH receptors, and CRH-BP in the wall of human normal and inflamed gallbladders, using RT-PCR and immunohistochemistry. Urocortin, but not CRH gene transcripts, was detected in RNA isolated from human gallbladder biopsy specimens. Urocortin immunoreactivity was localized in epithelial cells of the gallbladder mucosa. Gene expression of CRH(2) receptor was also detected, and the receptor protein had a localization similar to that of urocortin. Finally, CRH-BP gene expression and low levels of protein immunoreactivity were also shown. There were no differences in the expression profiles of all the above molecules between normal and inflamed tissues. In conclusion, the CRH system is present in the human gallbladder, urocortin being the major ligand expressed, possibly exerting an autocrine/paracrine biological role via activation of the CRH(2(alpha)) receptors found locally. Further study is required to enfold the biological role of these effectors in gallbladder physiology and pathogenesis.
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PMID:Urocortin and corticotropin-releasing hormone receptor type 2 expression in the human gallbladder. 1653 39

Urocortin (UCN), a newly identified, 40-amino-acid, corticotropin-releasing hormone (CRH) structurally related peptide, has been demonstrated to be expressed in the central nervous system and many peripheral tissues of rats and man. This study aimed to investigate the expression profile of UCN in rat lung and the effect of UCN on lung vascular permeability. The expression of UCN mRNA was detected by reverse transcriptase PCR (RT-PCR). UCN peptide was measured by immunohistochemistry and Western blot analysis. We found that both UCN mRNA and peptide were obviously expressed in rat lung. Immunohistochemistry results showed that UCN peptide is mainly expressed in bronchial epithelium mucosa and alveolar epithelium. We also found that rats receiving inhalation aerosol of UCN had a significant elevation of lung vascular permeability compared with rats receiving vehicle and ovalbumin (OVA) by the Evans blue (EB) technique. UCN aerosol inhalation resulted in obvious pulmonary congestion and edema observed under light microscope by hematoxylin and eosin (HE) staining. The nonselective peptide CRH receptor antagonist astressin markedly reduced lung vascular permeability triggered by UCN. Enhanced pulmonary vascular permeability induced by UCN was markedly inhibited by pretreatment with the mast-cell stabilizer cromolyn and histamine-1 (H1) receptor antagonist azelastine respectively, but not by the leukotriene receptor antagonist montelukast. In summary, in the present study, we demonstrated for the first time that UCN is expressed in rat lung and contributes to an increase in lung vascular permeability through activation of CRH receptors. Mast cells and histamine may be involved in this effect of UCN. Peripherally produced UCN in lung may act as an autocrine and paracrine proinflammatory factor.
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PMID:Expression of urocortin in rat lung and its effect on pulmonary vascular permeability. 1661 91

Urocortin 1, highly conserved metazoan gene of the corticotropin-releasing hormone family, is a simple gene structured in two exons and the corresponding intron. The urocortin 1 prepropeptide is entirely coded in the second exon. Preliminary non-isotopic in situ hybridization experiments with an oligonucleotide complementary to an intron sequence of the urocortin 1 gene showed a significant cytoplasmic-like staining, suggesting the occurrence of an intron-retained urocortin 1 transcript. This observation prompted us to study whether the urocortin 1 gene presents alternative splicing by intron retention event. Confocal fluorescent in situ hybridization for urocortin 1 RNA and the use of the specific DNA dye TOPRO-3 allowed us to show significant expression of the intron-retained urocortin 1 transcript that did not colocalize with TOPRO-3 staining indicating a cytoplasmic localization for the intron-retained urocortin 1 transcript. The natural occurrence of a polyadenylated intron-retained urocortin 1 RNA was further documented by reverse transcriptase polymerase chain reaction (PCR), primed with oligo(dT), of total RNA extracted from three brain regions, a midbrain region containing the Edinger-Westphal nucleus, cerebellum and prefrontal cortex. In the three brain regions studied, it was possible to amplify both intron-less as well as intron-retained urocortin 1 transcripts. The use of PCR primers that simultaneously amplify both urocortin 1 transcripts allowed us to show that the expression of both urocortin 1 transcripts differs among the brain regions analyzed, suggesting a tissue specific regulation of this alternative splicing. In silico analysis of the five known mammalian urocortin 1 genomic sequences showed high conservation of the urocortin 1 intron sequence. Further studies should investigate the regulation of this intron retention event and its consequence for the functionality of the urocortin 1 gene.
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PMID:Intron retention as an alternative splice variant of the rat urocortin 1 gene. 1665 Jun 5

Human skin is a local source of corticotropin-releasing hormone (CRH) and expresses CRH and CRH receptors (CRH-R) at mRNA and protein levels. Epidermal melanocytes respond to CRH by induction of cAMP with up-regulation of pro-opiomelanocortin gene expression and subsequent production of adrenocorticotropin hormone. However, the role of CRH/CRH-R in melanocyte biology is complicated by the significant heterogeneity of cutaneous melanocyte subpopulations, from continuously active and UV-responsive melanocytes in epidermis to UV nonresponsive, hair growth cycle-coupled melanogenesis in hair follicles. In the present study we report that normal human scalp hair follicle melanocytes express CRH at the mRNA level. Furthermore, CRH, urocortin and CRH-R 1 and 2 were differentially expressed in follicular melanocytes, fibroblasts, and keratinocytes depending on anatomic location and differentiation status in situ and in vitro. Stimulation of follicular melanocytes with CRH and CRH peptides, modified for selectivity for CRH-R1 and/or CRH-R2, variably induced cell melanogenesis, dendricity, and proliferation. CRH-peptides also stimulated the expression and activity of Tyrosinase, and expression of Tyrosinase-related protein-1 and-2. However, a modified urocortin peptide highly selective for CRH-R2 down-regulated melanocyte differentiation phenotype. This study indicates that CRH peptides can differentially influence hair follicle melanocyte behavior not only via CRH-R1 signaling but also by complex cross-talk between CRH-R1 and CRH-R2.
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PMID:Modulation of the human hair follicle pigmentary unit by corticotropin-releasing hormone and urocortin peptides. 1667 46

Urocortin (UCN) is a 40 amino acid peptide which is closely related to corticotropin-releasing hormone and binds with high affinity to both CRH type 1 and type 2 receptors. UCN is expressed in human reproductive tissues including endometrium, ovary, and placenta. This study was designed to investigate the cellular localization of UCN at the implantation site of the human blastocyst, as well as the regulation of the UCN promoter by two major intracellular signaling pathways, the cAMP/PKA and diacylglycerol/PKC pathways, in cells of placental origin. For this reason, immunohistochemistry was performed on tissue sections from paraffin-embedded human first trimester placentas and freshly isolated human invasive extravillous trophoblast cells (EVT) were analyzed for UCN expression using RT-PCR and immunofluorescence. Finally, UCN promoter activity was analyzed in the JEG3 human choriocarcinoma cell line. Immunohistochemistry revealed expression of UCN in the cytotrophoblast, the EVT and decidual cells. Both UCN mRNA and peptide were detectable in freshly isolated EVT. Finally, a human UCN promoter luciferase reporter construct transfected into JEG3 cells was significantly inducible by phorbol ester plus ionomycin, but not by phorbol ester alone or by forskolin. Collectively, the present study reports the expression of UCN in EVT and the activation of the UCN gene promoter by the diacylglycerol/PKC pathway. The functional significance of urocortin for the physiology of EVT requires further investigation.
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PMID:Expression of urocortin in the extravillous human trophoblast at the implantation site. 1669 78

Corticotropin releasing factor (CRF) is known to be involved in the stress response and in some degenerative brain disorders. In addition, CRF has a role as a neuromodulator in adult cerebellar circuits. Data from developmental studies suggest a putative role for CRF as a trophic factor during cerebellar development. In this study, we investigated the trophic role for CRF family of peptides by culturing cerebellar neurons in the presence of CRF, urocortin or urocortin II. Primary cell cultures of cerebella from embryonic day 18 mice were established, and cells were treated for either 1, 5 or 9 days with Basal Medium Eagles complete medium alone or complete medium with 1 microM CRF, urocortin, or urocortin II. The number of GABA-positive neurons in each treatment condition was counted at each culture age for monitoring the changes in neuronal survival. Treatment with 1 microM CRF or 1 microM urocortin increased the survival of GABAergic neurons at 6 days in vitro and 10 days in vitro, and this survival promoting effect was abolished by treatment with astressin in the presence of those peptides. Based on these data, we suggest that CRF or urocortin has a trophic role promoting the survival of cerebellar GABAergic neurons in cultures.
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PMID:Corticotropin-releasing factor (CRF) and urocortin promote the survival of cultured cerebellar GABAergic neurons through the type 1 CRF receptor. 1677 99


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