Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Delivery of cholesterol to inner mitochondrial membranes is rate-limiting for steroidogenesis in the zona fasciculata of adrenal cortex. A protein that stimulates this process was isolated to homogeneity from bovine adrenal tissue. This protein's primary structure has been determined in its entirety by a combination of automated Edman microsequencing, fast-atom bombardment mass spectrometry (FAB-MS). The sequence was identical to that previously reported for bovine brain endozepine, except that it lacks the last two residues, -Gly-Ile, at the C terminus. To our knowledge, isolation of an endozepine-related protein from a tissue other than brain has not been reported previously. Endozepine competes with benzodiazepines for saturable binding sites in synaptosomes and in mitochondria of specific peripheral tissues. Previous reports have localized the adrenal benzodiazepine receptor to the outer mitochondrial membrane. In this report, we show that the prototypic benzodiazepine, diazepam, effects a stimulation of adrenal mitochondrial cholesterol delivery similar to that observed for endozepine. The effective diazepam concentration was consistent with that previously shown to displace a high-affinity ligand of the mitochondrial benzodiazepine receptor. The action of diazepam in adrenal mitochondria suggests that the mediation of corticotropin-induced steroidogenesis may be the physiological function of the peripheral-type benzodiazepine receptor. These studies provide new insights into the previously unknown function of peripheral benzodiazepine receptors and should allow new investigations into the stimulation of steroidogenesis by endozepines and benzodiazepines in the brain and in certain peripheral tissues.
 ...
PMID:Identification of des-(Gly-Ile)-endozepine as an effector of corticotropin-dependent adrenal steroidogenesis: stimulation of cholesterol delivery is mediated by the peripheral benzodiazepine receptor. 254 79

It is theorized that intermediate filaments are important in the modulation of membrane activity and cell motility; however, their functions are unknown. The assembly and organization of these filaments are under hormonal regulation. We investigated in human monocytes the in vitro effects of Met-enkephalin, Leu-enkephalin, and beta-endorphin on the expression of immunoreactive cytoskeletal vimentin filaments. We simultaneously examined their effect on the phagocytosis of Candida albicans and on the membrane display of surface molecules. The three opioid peptides markedly reduced the expression of vimentin filaments, the phagocytic activity, and the display of HLA-DR molecules at concentrations of 10(-6), 10(-8), and 10(-10) M. On the other hand, the intravenous administration of fentanyl, a synthetic opiate agonist, to patients undergoing surgery induced similar changes in monocytes. In other experiments, 10(-8) M beta-endorphin also decreased the expression of CR3 but did not influence the display of CD13, a surface protein of unknown function. Expression of vimentin filaments correlated directly with the display of HLA-DR antigens and CR3 and with the phagocytic activity. The results of this paper indicate that opiates and opioids, neuropeptides known to be released during stress, can directly depress several monocyte functions. Furthermore, from these data it may be speculated that intermediate filaments may regulate the membrane expression of some surface molecules and the phagocytic process.
 ...
PMID:Opioid peptides modulate the organization of vimentin filaments, phagocytic activity, and expression of surface molecules in monocytes. 271 83

Beta-endorphin (beta-ED) levels were evaluated in blood and seminal plasma of men with infertility due to varicocele, obstructive and nonobstructive azoospermia, and idiopathic oligoasthenospermia. The relation of this opiate to serum levels of gonadotropins, prolactin, testosterone, androstenedione, and dehydroepiandrosterone sulfate has also been investigated. beta-ED levels in seminal plasma were significantly higher than in blood plasma (p less than 0.001) in all persons studied. No statistically significant differences were found for beta-ED concentrations in semen or blood among any of the infertility situations studied. Nor were significant correlations observed between the concentration of this opiate and that of gonadotropins, prolactin, and androgens. The measurement of beta-ED in semen has little value in the differential diagnosis of male infertility. Nonetheless, its presence in high levels in semen must have some unknown function. Possibly, it comes from the various sites of the male reproductive tract, since no significant differences were found between obstructive and nonobstructive azoospermias.
 ...
PMID:Beta-endorphin and male infertility. 294 70

N-Linked oligosaccharides terminating with the sequence SO(4)-4-GalNAcbeta1,4GlcNAcbeta1,2Manalpha are present on the pituitary hormones lutropin (LH), thyrotropin, and pro-opiomelanocortin. The sulfated structures on LH are essential for expression of its biologic function in vivo. We have cloned the N-acetylgalactosamine-4-sulfotransferase (GalNAc-4-ST1, GenBank(TM) accession number ), which mediates sulfate addition to the N-linked oligosaccharides on LH and other pituitary glycoproteins with terminal (beta1,4-linked GalNAc based on its homology to HNK-1 sulfotransferase (HNK-1 ST). GalNAc-4-ST1 displays 23% identity to HNK-1 ST and 28% to chondroitin 4-sulfotransferase 1 (C4ST-1) and 26% to chondroitin 4-sulfotransferase 2 (C4ST-2). The cDNA predicts a type II transmembrane protein of 424 amino acids with four potential N-linked glycosylation sites and a single membrane-spanning domain. GalNAc-4-ST1 has putative 5'-phosphosulfonate and 3'-phosphate binding sites. Three more carboxyl-terminal regions of unknown function also show a high degree of identity with HNK-1 ST, C4ST-1, and C4ST-2. The membrane-bound form of GalNAc-4-ST1 transfers sulfate to GalNAcbeta1, 4GlcNAcbeta-R but not to chondroitin, whereas truncated forms of GalNAc-4-ST1 that are released into the medium transfer sulfate to both GalNAcbeta1,4GlcNAcbeta-R and chondroitin. The first 118 amino acids of GalNAc-4-ST1 appear to contribute to both its activity and specificity for terminal beta1,4-linked GalNAc. GalNAc-4-ST1 also efficiently transfers sulfate to N-linked oligosaccharides on native LH and other glycoproteins terminating with beta1,4-linked GalNAc. A single transcript of 2.4 kilobases is most highly expressed in the pituitary and other regions of the central nervous system. The GalNAc-4-ST1 gene is located on human chromosome 19q13.1.
 ...
PMID:Molecular cloning and expression of the pituitary glycoprotein hormone N-acetylgalactosamine-4-O-sulfotransferase. 1098

Prader-Willi syndrome (PWS) is caused by loss of paternally expressed genes in the 15q11-q13 region. To further characterize alterations in gene expression in this classical obesity syndrome we used whole genome microarrays to study a PWS mouse model resulting from a paternally derived imprinting center (IC) deletion (PWS IC deletion). These mice die generally within 2-3 days of life (reflective of failure to thrive in infants with PWS) and therefore, the analysis was performed on RNA extracted from the whole brain of PWS IC deletion mice and normal littermates at less than 24 hr after birth. Of more than 45,000 probes examined, 26,471 (59%) were detected for further analysis, and 69 had a significant change in expression of at least 1.5-fold and a false discovery rate (FDR) of 5%. Eight of the genes with differential expression were imprinted and from the PWS critical region (PWSCR). The three genes with the highest expression in the PWS IC mice were pro-opiomelanocortin (Pomc) and two transcripts of unknown function. Pomc knockout mice have been shown to develop obesity. Therefore, elevated Pomc RNA in PWS IC deletion neonatal mice may be an important genetic factor in the survival of these mice as it may affect eating behavior. Interestingly, Mc5r, a melanocortin receptor known to directly respond to Pomc expression changes, was upregulated as well. Mc5r is known to be involved with thermoregulation which is reportedly abnormal in PWS infants. These observations support a role for Pomc and the network of genes involved in regulating energy homeostasis in the early clinical findings of failure to thrive observed in PWS. Other notable patterns include three previously unstudied transcripts that are expressed only from the paternal allele under regulatory control of the IC and include AK013560, BB3144814, and BB182944 (whose genes are located in the mouse PWSCR on chromosome 7B). As expected, all the known paternally expressed genes from the PWSCR had detection signals below the threshold in the PWS IC deletion mice but were clearly detectable in control littermates. Several of the genes in this study were further examined by quantitative reverse transcription-PCR (RT-PCR) to confirm their expression status. Further analysis of gene expression in these mice may lead to novel pathways affected in PWS. These results, along with other recent reports, suggest that the cumulative effect of modest changes in expression of many genes, especially genes involved in energy metabolism, contribute to the failure to thrive of infants with PWS.
 ...
PMID:Whole genome microarray analysis of gene expression in an imprinting center deletion mouse model of Prader-Willi syndrome. 1703 36

Mimecan is a protein of unknown function that is expressed in the pituitary tissues of mouse and human. In this study, we observed the function of mimecan on the proopiomelanocortin (POMC) gene in the pituitary and the hypothalamo-pituitary-adrenal axis (HPAA). Incubating pituitary corticotroph AtT-20 cells with recombinant mimecan protein stimulated adrenocorticotrophic hormone (ACTH) secretion without significantly up-regulating POMC gene expression. In addition, pituitary corticotroph AtT-20 cell corticotropin-releasing hormone receptor 1 (CRHR1) gene expression was induced by mimecan. Interestingly, long-term mimecan overexpression in corticotroph cells increased CRHR1 mRNA levels while slightly decreasing POMC mRNA expression and ACTH secretion. Using mimecan knockout mice, we found that, although the serum ACTH concentration was not significantly different between wild type and mimecan knockout mice under basal conditions, the serum ACTH level was relatively lower in mimecan knockout mice after treatment with corticotropin-releasing hormone (CRH). Meanwhile, we observed that POMC and CRHR1 gene expression decreased in primary cultured knockout mouse pituitary cells compared with wild type cells. Taken together, these data suggest that mimecan expressed in pituitary corticotroph cells mainly regulates ACTH secretion in the pituitary and coordinates the HPAA.
 ...
PMID:Mimecan in pituitary corticotroph cells may regulate ACTH secretion and the HPAA. 2166 48

A transcript of unknown function, regulated by fasting and feeding, was identified by microarray analysis. The transcript is up-regulated in the fasting state. An 1168-bp cDNA was cloned from rat hypothalamus and sequenced. This sequence is consistent with adipogenesis down-regulating transcript 3 (AGD3) (also known as human OCC-1) mRNA. A protein sequence identical to AGD3 was determined by mass spectrometry. In the rat brain, AGD3 mRNA is distributed in the arcuate nucleus, ventromedial hypothalamus, amygdaloid nuclei, hippocampus, and somatic cortex. Double in situ hybridisation showed that AGD3 mRNA is co-localised with pro-opiomelanocortin and neuropeptide Y in arcuate nucleus neurones. AGD3 binds with insulin receptor substrate 4 and increases insulin-stimulated phospho-Akt and regulates AMP-activated protein kinase and mammalian target of rapamycin downstream target S6 kinase phosphorylation.
 ...
PMID:A novel transcript is up-regulated by fasting in the hypothalamus and enhances insulin signalling. 2293 15

TMEFF2 is a transmembrane protein with unknown function, containing an altered epidermal growth factor (EGF)-like motif, two follistatin-like domains, and a cytosolic tail with a putative G-protein-activating motif. TMEFF2 is predominantly expressed in brain and prostate and has been implicated in cell signaling, neuronal cell survival, and tumor suppression. We found that expression of TMEFF2 in pituitary corticotrope cells inhibits the effects of corticotropin-releasing hormone (CRH) on the production of intracellular cAMP, and CREB, and transcription of Pomc. Regulation of the activity of CRH by TMEFF2 requires neither the cytoplasmic tail nor the EGF domain, while deletion of the follistatin modules abolishes the inhibitory function of TMEFF2. Moreover, a soluble secreted protein containing the complete extracellular domain is sufficient for inhibition of CRH signaling. TMEFF2-induced inhibition depends on serum components. Furthermore, TMEFF2 regulates the non-canonical activin/BMP4 signaling, PI3K, and Ras/ERK1/2 pathways. Thus, TMEFF2 inhibits the CRH signaling pathway and the PI3K/AKT and Ras/ERK1/2 pathways, contributing to a significant inhibition of transcription of Pomc. We found that expression of TMEFF2 in human Cushing's adenoma is reduced when compared with normal human pituitary, which may indicate that TMEFF2 acts as a tumor suppressor in these adenomas. Furthermore, the overexpression of TMEFF2 decreased proliferation of corticotrope cells. Our results indicate a potential therapeutic use of TMEFF2 or factors that stimulate the activity of TMEFF2 for the treatment of corticotrope tumors in order to reduce their secretion of ACTH and proliferation.
...
PMID:TMEFF2 is an endogenous inhibitor of the CRH signal transduction pathway. 2557 2

A subset of corticotropin-releasing hormone (CRH) neurons was previously identified in the hippocampus with unknown function. Here we demonstrate that hippocampal CRH neurons represent a novel subtype of interneurons in the hippocampus, exhibiting unique morphology, electrophysiological properties, molecular markers, and connectivity. This subset of hippocampal CRH neurons in the mouse reside in the CA1 pyramidal cell layer and tract tracing studies using AAV-Flex-ChR2-tdTomato reveal dense back-projections of these neurons onto principal neurons in the CA3 region of the hippocampus. These hippocampal CRH neurons express both GABA and GAD67 and using in vitro optogenetic techniques, we demonstrate that these neurons make functional connections and release GABA onto CA3 principal neurons. The location, morphology, and importantly the functional connectivity of these neurons demonstrate that hippocampal CRH neurons represent a unique subtype of hippocampal interneurons. The connectivity of these neurons has significant implications for hippocampal function.
 ...
PMID:Characterization of a novel subtype of hippocampal interneurons that express corticotropin-releasing hormone. 2613 56