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)

Diazepam-binding inhibitor (DBI) is a 9-kDa polypeptide that colocalizes in glial, adrenocortical, and Leydig cells with the mitochondrial DBI receptor (MDR). By binding with high affinity to the MDR, DBI and one of its processing products--DBI-(17-50)--regulate pregnenolone synthesis and have been suggested to participate in the immediate activation of adrenal steroidogenesis by adrenocorticotropic hormone (ACTH). In adrenals of hypophysectomized rats (1 day after surgery), ACTH failed to acutely affect the amount of adrenal DBI and the density of MDR but increased the rate of DBI processing, as determined by the HPLC profile of DBI-(17-50)-like immunoreactivity. The similar latency times for this effect and for ACTH stimulation of adrenal steroidogenesis suggest that the two processes are related. The ACTH-induced increase in both adrenal steroidogenesis and rate of DBI processing were completely inhibited by cycloheximide; this result suggests the requirement for the de novo synthesis of a protein with a short half-life, probably an endopeptidase. This enzyme, under the influence of ACTH, may activate formation of a DBI-processing product that stimulates steroidogenesis via the MDR. In support of this hypothesis is the demonstration that in hypophysectomized rats the MDR antagonist PK 11195 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxam ide completely inhibited the adrenal steroidogenesis stimulated by ACTH and by the high-affinity MDR ligand 4'-chlorodiazepam.
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PMID:Diazepam-binding inhibitor (DBI)-processing products, acting at the mitochondrial DBI receptor, mediate adrenocorticotropic hormone-induced steroidogenesis in rat adrenal gland. 127 86

Congenital lipoid adrenal hyperplasia is the most severe form of congenital adrenal hyperplasia. Affected individuals can synthesize no steroid hormones, and hence are all phenotypic females with a severe salt-losing syndrome that is fatal if not treated in early infancy. All previous studies have suggested that the disorder is in the cholesterol side chain cleavage enzyme (P450scc), which converts cholesterol to pregnenolone. A newborn patient was diagnosed by the lack of significant concentrations of adrenal or gonadal steroids either before or after stimulation with corticotropin (ACTH) or gonadotropin (hCG). The P450scc gene in this patient and in a previously described patient were grossly intact, as evidenced by Southern blotting patterns. Enzymatic (polymerase chain reaction) amplification and sequencing of the coding regions of their P450scc genes showed these were identical to the previously cloned human P450scc cDNA and gene sequences. Undetected compound heterozygosity was ruled out in the new patient by sequencing P450scc cDNA enzymatically amplified from gonadal RNA. Northern blots of gonadal RNA from this patient contained normal sized mRNAs for P450scc and also for adrenodoxin reductase, adrenodoxin, sterol carrier protein 2, endozepine, and GRP-78 (the precursor to steroidogenesis activator peptide). These studies show that lipoid CAH is not caused by lesions in the P450scc gene, and suggest that another unidentified factor is required for the conversion of cholesterol to pregnenolone, and is disordered in congenital lipoid adrenal hyperplasia.
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PMID:Normal genes for the cholesterol side chain cleavage enzyme, P450scc, in congenital lipoid adrenal hyperplasia. 166 Dec 94

Acyl-coenzyme A binding protein from bovine liver and the protein expressed in Escherichia coli by the recombinant gene of this protein have been studied by two-dimensional 1H nuclear magnetic resonance spectroscopy. This protein has, in addition to the ability to bind acyl-coenzyme A, been reported to have several important physiological and biochemical functions. It is known as the diazepam binding inhibitor, as a putative neurotransmitter, as a regulator of insulin release from pancreatic cells, and as a mediator in corticotropin-dependent adrenal steroidogenesis. The only difference between the protein produced by recombinant techniques and the native acyl-coenzyme A binding protein is the N-terminal acetyl group present only in the native protein. The two proteins have 86 amino acid residues and a molecular mass of approximately 10,000 Da. Complete assignment of the 1H nuclear magnetic resonances has been obtained for a major proportion of the amino acid residues (55 residues), and partial assignment has been achieved for the others (31 residues). Sequential nuclear Overhauser effects have demonstrated that the protein has a secondary structure consisting of four alpha-helices of residues 1-15, 22-35, 52-60, and 68-85. Furthermore, a large number of long-range nuclear Overhauser effects have been identified, indicating that the assignment given here will provide a basis for a structure determination of this protein in solution by nuclear magnetic resonance spectroscopy.
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PMID:The secondary structure in solution of acyl-coenzyme A binding protein from bovine liver using 1H nuclear magnetic resonance spectroscopy. 193 85

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.
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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

Diazepam-binding inhibitor (DBI) is a neuromodulatory peptide for gamma-aminobutyric acid (GABA) neurotransmission. Cerebrospinal fluid (CSF) levels of DBI have been found to be elevated in depression. CSF levels of the peptide corticotropin-releasing hormone (CRH) have also been found to be elevated in depression. Therefore, we examined for a relationship between DBI and CRH in human CSF. We found significant positive correlations between CSF levels of DBI and CRH in depressed patients, pathological gamblers, and normal controls. These data, along with the elevated CSF levels of DBI in depression, suggest the possibility that DBI may have a role in coordinating responses to stress in humans in addition to its possible role in the pathophysiology of depression.
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PMID:Diazepam-binding inhibitor and corticotropin-releasing hormone in cerebrospinal fluid. 281 71

In order to evaluate the regulation of neuropeptide stores in structures of the rat brain, the content of the specific messenger ribonucleic acid for the peptide precursor, of the precursor and of its biologically active peptide fragment, resulting from the precursor processing was measured. Enkephalin stores of the striatum, but not that of other structures, were upregulated by repeated daily doses of dopaminergic receptor antagonists of the D-1 type. Morphine tolerance failed to change stores of enkephalin in brain but produced a down-regulation of the synthesis of pro-opiomelanocortin in the hypothalamus. The regulation of diazepam binding inhibitor (DBI), the precursor of a family of putative endogenous ligands of the benzodiazepine recognition site, was studied during tolerance to benzodiazepines. Tolerance to diazepam increased the dynamic state of an octadecaneuropeptide (ODN), derived from DBI, in the cerebellum and cortex. The steady state or dynamic state of ODN were not changed in other structures of the brain of the rat, tolerant to diazepam.
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PMID:In vivo studies of the regulation of neuropeptide stores in structures of the rat brain. 282 28

The neuropeptides diazepam binding inhibitor (DBI) and corticotropin-releasing hormone (CRH) elicit anxietylike symptoms when administered intracerebroventricularly to laboratory animals. Because of the similarities between the symptoms of certain anxiety states and the alcohol withdrawal syndrome, we hypothesized that increased secretion of either of these endogenous neuropeptides may, at least in part, be responsible for the symptoms of alcohol withdrawal. We therefore measured DBI and CRH concentrations in cerebrospinal fluid (CSF) of 15 alcohol-dependent patients during acute withdrawal (Day 1) and again at 3 week's abstinence (Day 21). In addition, plasma concentrations of cortisol were measured to evaluate the relationship between pituitary-adrenal axis activation and CSF CRH concentrations. CSF CRH (p < .04), but not CSF DBI, was significantly higher on Day 1 than on Day 21. Although there was a significant decrease in plasma cortisol from Day 1 to Day 21 (p < .001), a significant correlation between CSF CRH and plasma cortisol concentrations was not observed at either time point. Neither CSF neuropeptide correlated with clinical measures of withdrawal severity. These tentative findings may implicate CRH, but not DBI, in the pathogenesis of alcohol withdrawal. Alternately, the central release of CRH and DBI may not be adequately reflected in lumbar CSF.
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PMID:Cerebrospinal fluid concentrations of corticotropin-releasing hormone (CRH) and diazepam-binding inhibitor (DBI) during alcohol withdrawal and abstinence. 887 12

We have recently demonstrated that the endozepine octadecaneuropeptide (ODN) exerts an inhibitory influence on corticotropin-releasing hormone (CRH) mRNA expression. The effect is mediated by GABAA receptors and is reversed by adrenalectomy. In order to investigate the involvement of peripheral steroids and more particularly of glucocorticoids in the ODN modulation of CRH mRNA expression, we have evaluated, in adrenalectomized and castrated male rats (ADX/CX), the effect of dexamethasone (DEX) pretreatment on CRH mRNA expression induced by central injection of ODN. Variations in the CRH mRNA expression in the hypothalamic paraventricular nucleus have been studied using quantitative in situ hybridization. The intracerebroventricular injection of ODN (4 microg/kg), as previously reported, induced a significant inhibition of CRH mRNA expression in sham-operated rats (-33%). This inhibition was reversed in ADX/CX male rats (+65% vs. sham vehicle-injected rats and +20% vs. ADX/CX vehicle-injected rats). Pretreatment with DEX (5 mg/kg) during 4 days induced in ADX/CX rats a decrease of 22% (vs. ADX/CX vehicle-injected rats) in the CRH mRNA signal, which became comparable to that observed in sham vehicle-injected rats. Pretreatment of ADX/CX animals with DEX prevented the ODN-induced increase in CRH mRNA expression, inducing rather a 16 and 30% inhibition when compared to vehicle- and ODN-injected ADX/CX rats, respectively. Moreover the CRH mRNA levels observed in ODN-injected ADC/CX rats were higher than those observed in sham vehicle- and sham ODN-injected rats (+16% vs. sham vehicle-injected rats and +63% vs. sham ODN-injected rats). These results indicate that dexamethasone treatment in ADX/CX rats can restore mRNA levels to those observed in sham-operated animals but not the inhibiting effect induced by ODN. Together with previous findings, these results suggest that adrenal and/or gonadal factor(s) other than glucocorticoids are involved in ODN modulation of the HPA axis.
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PMID:Role of glucocorticoids in the modulation of corticotropin-releasing hormone mRNA level by the endogenous benzodiazepine receptor ligand octadecaneuropeptide in rat brain. 970 76

Intracerebroventricular (i.c.v.) administration of the octadecaneuropeptide (diazepam-binding inhibitor [33-50]; ODN) exerts a potent anorexigenic effect in the rat. We studied the effect of ODN on three neuropeptides involved in feeding behaviour: the orexigenic peptide neuropeptide Y (NPY) and two anorexigenic peptides, corticotropin-releasing hormone (CRH) and the pro-opiomelanocortin (POMC)-derived peptide alpha-melanocyte-stimulating hormone. The effect of i.c.v. administration of ODN (0.1 microg/kg and 1 microg/kg) on mRNA expression of the peptides in male rat hypothalamus was evaluated by semiquantitative in situ hybridization. In the arcuate nucleus, NPY-expressing neurones were mostly found in the inner zone in close proximity of the third ventricle. ODN at the dose of 0.1 microg/kg induced a significant decrease of 17.4% in NPY mRNA expression, while the depressing effect was more marked (31.4%) with the highest dose of ODN (1 microg/kg). POMC-expressing neurones were more laterally located in the arcuate nucleus. Administration of ODN at 0.1 microg/kg and 1 microg/kg doses induced increases of 33.5% and 27.4% in POMC mRNA expression, respectively. Labelling obtained with the CRH cRNA probe was essentially distributed throughout the medial parvocellular area of the hypothalamic paraventricular nucleus. ODN, at doses of 0.1 and 1 microg/kg, resulted in 17.8% and 32.8% decreases in CRH mRNA expression, respectively. The present data suggest that ODN might exert its anorexigenic effect by increasing mRNA expression of POMC and decreasing mRNA expression of NPY in the arcuate nucleus.
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PMID:Effect of intracerebroventricular administration of the octadecaneuropeptide on the expression of pro-opiomelanocortin, neuropeptide Y and corticotropin-releasing hormone mRNAs in rat hypothalamus. 1253 62

Intracerebroventricular (ICV) administration of the octadecaneuropeptide (ODN), a peptide derived from diazepam-binding inhibitor, reduces food intake in goldfish as in rodents. However, the neurochemical pathways involved in the anorexigenic action of ODN have not yet been identified in goldfish. Alpha-melanocyte-stimulating hormone (alpha-MSH), corticotropin-releasing hormone (CRH), and CRH-related peptides play a major role in the control of food consumption in goldfish. In this species, the anorexigenic action of alpha-MSH is mediated via the CRH/CRH receptor neuronal system. Therefore, in the present study, we examined whether the anorexigenic effect of ODN in goldfish could be mediated through alpha-MSH and/or CRH neuronal pathways. ICV injection of ODN (10 pmol/g body weight (BW)) significantly reduced food intake, and the anorexigenic effect of ODN was suppressed by ICV preinjection of the melanocortin 4 receptor (MC4R) antagonist HS024 (40 pmol/g BW) or the CRH receptor 1/receptor 2 antagonist alpha-helical CRH((9-41)) (100 pmol/g BW). ICV injection of ODN (10 pmol/g BW) induced a significant increase of proopiomelanocortin mRNA level but had no effect on CRH mRNA level, while ICV injection of the MC4R agonist, melanotan II (100 pmol/g BW), significantly enhanced CRH mRNA expression. These results suggest that, in goldfish, the anorexigenic action of ODN is mediated by the MC4R- and subsequently through the CRH receptor-signaling pathways.
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PMID:The anorexigenic action of the octadecaneuropeptide (ODN) in goldfish is mediated through the MC4R- and subsequently the CRH receptor-signaling pathways. 2030 9


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