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)

We evaluated the effects of intracerebroventricular (i.c.v.) administration of beta-endorphin and naloxone, an opioid antagonist, on the induction of c-fos and corticotropin-releasing factor (CRF) mRNA to clarify the effects of beta-endorphin on cellular activity and CRF gene expression in the paraventricular nucleus (PVN) of the rat using in situ hybridization. A significant induction of c-fos mRNA was noted in the PVN after i.c.v. injection of beta-endorphin, compared to control. This induction was inhibited by the administration of naloxone. A significant increase in CRF mRNA levels in the PVN was observed 120 min after the i.c.v. injection of beta-endorphin. This increase was partially, but significantly, inhibited by naloxone administration. In addition, i.c.v. administration of beta-endorphin increased plasma ACTH concentration in freely moving rats, which was inhibited by intravenous injection of CRF antiserum. These results suggest that the i.c.v. injection of beta-endorphin increases the neuronal activity and the biosynthesis of CRF in the PVN, and stimulates the secretion of ACTH by increasing CRF secretion. This effect on the PVN was mediated, at least in part, via the opioid receptor.
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PMID:Intracerebroventricular administration of beta-endorphin increases the expression of c-fos and of corticotropin-releasing factor messenger ribonucleic acid in the paraventricular nucleus of the rat. 891 95

5-Hydroxytryptamine-1A (5-HT1A) receptor agonists, including flesinoxan, reduce anxiety and activate the hypothalamus-pituitary-adrenal (HPA) axis under basal conditions. In order to investigate the underlying neural mechanisms we investigated immunoreactivity for the immediate early gene protein product Fos (Fos-ir) in rat brains 1 h after flesinoxan treatment (0.0, 0.3 or 3.0 mg/kg p.o.). Typically, 5-HT1A receptor-containing brain areas, such as the dorsal raphe nuclei, hippocampus, septum, diagonal band and the cortical and basomedial amygdala, do not show Fos-ir. Apparently, binding of flesinoxan at the 5-HT1A receptor does not directly lead to activation of c-fos in the cell, probably due to its negative coupling to adenylate cyclase. However, in typically non-5HT1A receptor-containing brain areas Fos-ir is increased due to flesinoxan treatment, as in the paraventricular nucleus of the hypothalamus (PVN), the dorsolateral part of the bed nucleus of the stria terminalis (BNSTdl) and the central amygdala (CeA). Flesinoxan-treated rats also exhibited higher plasma corticosterone levels than vehicle-treated animals, which suggests the involvement of corticotropin-releasing hormone (CRH) or vasopressin in the hypothalamus. After double immunolabelling (Fos/CRH or Fos/vasopressin), every CRH neuron detected in the PVN also contained Fos. Moreover, a significant correlation existed between the number of Fos-ir neurons in the PVN and the plasma corticosterone level. Hardly any Fos/vasopressin double labelling was visible in the PVN. Accordingly, flesinoxan exerts its activating effects on the HPA axis via CRH neurons in the PVN. These effects are trans-synaptically mediated by other brain areas, such as the CeA and BNSTdl, which also show increased Fos-ir.
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PMID:5-HT1A receptor agonist flesinoxan enhances Fos immunoreactivity in rat central amygdala, bed nucleus of the stria terminalis and hypothalamus. 895 98

The purpose of this study was to investigate whether the ovulatory cycle interferes with the effect of the acute-phase response of a systemic immune activation on the transcription of the immediate early gene c-fos and the stress-related neuropeptide corticotropin-releasing hormone (CRH) in the brains of female rats. Throughout the day of proestrus and diestrus-2 (09.00, 12.00, 15.00 h), adult rats received either a single intraperitoneal injection of the endotoxin lipopolysaccharide (LPS, 200 micrograms/100 g body weight) or the vehicle solution and were killed 3 h later (12.00, 15.00, 18.00 h). Frozen brains were mounted on a microtome, cut in 30-micron slices and then processed for the detection of c-fos mRNA and CRH primary transcript (heteronuclear [hnRNA]) by means of in situ hybridization histochemistry using 35S-labeled exonic and intronic probes, respectively. LPS injection induced a profound expression of c-fos mRNA in the several nuclei and areas of the brain, such as the organum vasculosum of the lamina terminalis/medial preoptic area, supraoptic nucleus, parvo- and magnocellular divisions of the hypothalamic paraventricular nucleus (PVN), arcuate nucleus/median eminence, central nucleus of the amygdala, locus coeruleus, nucleus of the solitary tract, area postrema and ventrolateral medulla. Interestingly, the intensity of expression of c-fos mRNA depended on the phase of the estrous cycle and/or the time of the day. Indeed, in several of the structures described above, LPS induced a more pronounced c-fos signal in the morning of proestrus than the afternoon and diestrus-2. CRH primary transcript was significantly increased by LPS treatment selectively in the parvocellular division of the PVN and the highest hybridization signal was observed in the morning of proestrus, a period where a large number of c-fos-positive cells were colocalized in CRH-immunoreactive neurons. A significant increase in the levels of AVP hnRNA was also observed in the parvocellular PVN of animals sacrificed at noon and early afternoon of both pro- and diestrus days. These results provide evidence that the neuroendocrine events regulating the reproductive cyclicity influence the endotoxin-induced activation of the early gene c-fos in selective structures of the brain and the stimulation of neurons directly involved in the regulation of the HPA axis. It is possible that the gonadal status of female mammals plays a crucial role in the integration of the organism in the presence of foreign material in preventing an exaggerated immune response during particular phases of the ovulatory cycle. The capacity of female animals to modulate the intensity through which the neuronal circuitry activated during immunogenic processes is likely to be an elegant sexual dimorphism participating in the adjustment of the responses in line with the physiological demand.
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PMID:Influence of the estrous cycle on c-fos and CRH gene transcription in the brain of endotoxin-challenged female rats. 903 72

Using murine AtT20 pituitary cells transfected with a rat pro-opiomelanocortin (POMC) promoter (-706/+64) linked to the luciferase reporter, we showed leukemia inhibitory factor (LIF) to strongly potentiate corticotropin-releasing hormone (CRH) induction of POMC gene expression. We therefore tested mechanisms for molecular interactions between LIF and CRH. Although LIF and CRH synergized to induce an 8-fold induction of POMC transcription, CRH alone (but not LIF) induced cAMP response element-binding protein phosphorylation (5-fold) or an increase of c-fos mRNA levels (>100-fold), suggesting that these pathways are not implicated in LIF transcriptional synergistic effects. Using a DNase I footprint assay, POMC promoter regions protected by AtT20 cell nuclear extracts were identified (-121/-109, and -143/-134, and -173/-160). The protected -173/-160 element fused to a heterologous promoter conferred LIF-CRH synergy (6.5-fold induction of POMC) and formed a specific complex with AtT20 cell nuclear extracts. This complex was supershifted by an anti-phosphoserine antibody, and a serine/threonine kinase inhibitor also altered both this complex and LIF-CRH transcriptional synergy on the POMC promoter-luciferase reporter construct, indicating that these events depend on post-translational serine phosphorylations. LIF-CRH synergy on POMC transcription is therefore mediated at least in part by -173/-160 sequences conferring confluent transcriptional activity of both peptides.
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PMID:A common pro-opiomelanocortin-binding element mediates leukemia inhibitory factor and corticotropin-releasing hormone transcriptional synergy. 909

C-fos expression appears in some activated cell types. Because of dynamic changes in gonadotropes during the estrous cycle, this study was initiated to determine if fos might be expressed in gonadotropes before any period of activation. We detected c-fos and pituitary antigens in dissociated anterior pituitary cells by dual-labeling immunocytochemistry. The highest percentage of cells with fos protein were found in proestrous rat populations. In diestrous and proestrous populations, dual labeling showed that 6-9% of pituitary cells contained fos with adrenocorticotropin, thyroid-stimulating hormone, prolactin, or growth hormone antigens. In contrast, only 0.8-3% contained fos with luteinizing hormone (LH) or follicle-stimulating hormone (FSH) antigens. We then tested the hypothesis that gonadotropes might increase fos expression earlier in the cycle. In populations from metestrous rats, c-fos labeling was found in 45% of LH cells compared to only 23% of LH cells in the proestrous group. This suggests that proportionately more LH cells are being activated to produce fos early in the cycle. Perhaps fos is used in translation of LH beta antigens or gonadotropin-releasing hormone (GnRH) receptor mRNAs. In contrast, less than 1% of all pituitary cells expressed fos with FSH at all stages of the cycle (only 6-12% of FSH cells). This differential expression suggests one mechanism behind the regulation of non-parallel storage and release of gonadotropin antigens.
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PMID:Differential expression of c-fos in vitro by all anterior pituitary cell types during the estrous cycle: enhanced expression by luteinizing hormone but not by follicle-stimulating hormone cells. 919 64

Lipopolysaccharide (LPS) is a potent stimulator of the hypothalamic-pituitary-adrenal (HPA) axis. However, the alteration in the HPA axis responsiveness and brain corticosteroid receptor levels during long-term administration of LPS has not been studied well. The present study was designed to examine the effect of single vs. repeated intraperitoneal (i.p.) LPS injection on the HPA axis and brain corticosteroid receptor levels in male Wistar rats. In addition, c-fos mRNA expression was examined in the hypothalamic paraventricular nucleus (PVN) and brainstem catecholaminergic nuclei such as the locus coeruleus (LC) and nucleus tractus solitarius (NTS), the sites known to be involved in LPS-induced HPA axis stimulation. Rats that had received i.p. LPS injection for 6 consecutive days (6-LPS group) had similar levels of plasma adrenocorticotropin (ACTH) and corticosterone (CORT) compared to animals that had received i.p. saline (6-saline group). A single injection of LPS to the 6-saline group (6-saline + challenge) resulted in a substantial increase in plasma ACTH and CORT at 2 h, whereas an additional injection of LPS to the 6-LPS group (6-LPS + challenge) showed less of an increase. As determined by in situ hybridization histochemistry, proopiomelanocortin (POMC) mRNA levels in the anterior pituitary (AP) and corticotropin-releasing hormone (CRH) mRNA levels in the PVN were higher in the 6-LPS than in the 6-saline group. A single injection of LPS to the 6-saline group resulted in a significant increase in AP POMC mRNA and PVN CRH mRNA at 2 h, while injection of LPS to the 6-LPS group showed no additional increase in these levels. C-fos mRNA expression was prominent in the PVN, LC, and NTS following a single injection of LPS, but not following repeated LPS injection. These results suggest that stimulatory input into the PVN decreased following repeated LPS injection. Furthermore, type II glucocorticoid receptor (GR) mRNA levels in the 6-LPS and 6-LPS + challenge groups were decreased in the hippocampus, but not in the PVN or AP. Adrenalectomy with 40% CORT pellet replacement restored ACTH responses following repeated LPS injections to levels similar to those following a single LPS injection. Decreased hippocampal GR mRNA may contribute to the elevated PVN CRH mRNA levels in the 6-LPS group. Nevertheless, inhibition of the pituitary ACTH response by glucocorticoids and reduced hypothalamic drive are partly responsible for decreased pituitary-adrenal responsiveness following repeated LPS injection.
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PMID:Hypothalamic-pituitary-adrenocortical responses to single vs. repeated endotoxin lipopolysaccharide administration in the rat. 936 46

Central administration of corticotropin-releasing hormone (CRH) induces immediate-early gene (IEG) expression (c-fos and NGFI-B) in forebrain structures in a pattern similar to that observed following restraint stress. Lactating rats display modified neuroendocrine and behavioural responses to stress which have been hypothesized to be at least partially mediated through changes within the circuitry converging on the PVN, including CRH activated pathways. Quantitative measures of regional expression of c-fos and NGFI-B mRNA representative of two classical intracellular pathways, were used to define modification of the circuitry involved in the altered response to central CRH in the lactating female. Compared to saline controls, virgin female rats injected with 5 micrograms CRH i.c.v. displayed significantly increased immediate-early gene expression in the hypothalamic paraventricular nucleus (PVN), arcuate nucleus, lateral septum, bed nucleus of the stria terminalis, central, medial and cortical nuclei of the amygdala, and all subfields of the hippocampal formation. In lactating rats treated with CRH there was a significant increase in c-fos gene expression in the CeA and in the hippocampal subfields CA1, CA4 and dentate gyrus but not in the other areas examined. The i.c.v. administration of CRH significantly increased NGFI-B expression in the PVN, arcuate nucleus, medial amygdala and all hippocampal subfields of virgin rats. Lactating rats treated with CRH failed to show a significant increase in NGFI-B expression in the PVN, median eminence, arcuate nucleus, medial amygdala, CA2 and CA3 subfields of the hippocampus. These results further suggest that changes in specific neural circuits might at least partially underlie the modified responses to CRH and perhaps to stress in the lactating female.
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PMID:Region-specific immediate-early gene expression following the administration of corticotropin-releasing hormone in virgin and lactating rats. 937 14

The activity of hypothalamic pro-opiomelanocortin (POMC) neurons is known to display a circadian cycle. We hypothesized that the existence of a c-Fos responsive element (AP-1 site) within the POMC gene sequence might reflect the ability of POMC neurons to express c-fos proto-oncogene during circadian increase of their neuronal activity. To this aim, adult male rats previously kept under a controlled 12 h light/12 h dark schedule were sacrificed every 4 h throughout the 24 h cycle and their brains processed for Fos and/or POMC immunocytochemistry. Here we show that, specifically during the dark period of the cycle, the mediobasal hypothalamic area spontaneously exhibits a strong Fos immunoreactivity, whereas very low Fos labelling was detected during the light period. As postulated, the simultaneous visualisation of both Fos and POMC antigens allowed us to show that this nocturnal induction of Fos occurs almost exclusively at the nuclear level of POMC-producing neurons. These results not only highlight the mechanisms underlying the physiological functioning of the hypothalamic POMC system, but also demonstrate the feasibility of using c-fos expression as a useful tool to assess the pharmacological effect of drugs on the activity of POMC neurons as is the case for many other neuronal systems. Such drugs might be relevant in the treatment of psychosis since an alteration of POMC-related peptide transmission has been reported in the brains of both schizophrenic and depressive patients.
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PMID:Daily cycle of fos expression within hypothalamic POMC neurons of the male rat. 938 7

Stimulation of the cornea activates neurons in two distinct regions of the spinal trigeminal nucleus: at the transition between trigeminal subnucleus interpolaris and subnucleus caudalis and at the transition between trigeminal subnucleus caudalis and the upper cervical spinal cord as estimated by expression of the immediate early gene, c-fos. To determine if receptors for substance P or neurokinin A, neurokinin 1 and neurokinin 2 receptors, respectively, contribute to the production of Fos-positive neurons in these brainstem regions, receptor-selective antagonists were given intracerebroventricularly 15 min prior to stimulation of the cornea in anesthetized rats. The number of Fos-positive neurons produced in superficial laminae at the trigeminal subnucleus caudalis/cervical cord transition by application of the selective small fiber excitant, mustard oil, to the corneal surface was reduced by the neurokinin 1 receptor antagonist, CP99,994 (5-100 nmol, i.c.v.) and the neurokinin 2 receptor antagonist, MEN10,376 (0.01-1.0 nmol, i.c.v.). Combined pretreatment with CP99,994 and the competitive N-methyl-D-aspartate receptor antagonist, CPP, caused a greater reduction in c-fos expression at the subnucleus caudalis/cervical cord transition than after either drug alone suggesting interaction between receptors for glutamate and substance P. Tachykinin receptor antagonists did not reduce the number of Fos-positive neurons produced at the subnucleus interpolaris/subnucleus caudalis transition. The elevation in plasma concentration of adrenocorticotropin, but not the increases in arterial pressure or heart rate, evoked by corneal stimulation was prevented by pretreatment with CP99,994 or MEN10,376 at doses lower than those needed to reduce c-fos expression. The results indicate that receptors for substance P and neurokinin A contribute to the transmission of sensory input from corneal nociceptors to brainstem neurons in trigeminal subnucleus caudalis and to increased activity of the hypothalamo-pituitary axis that accompanies acute stimulation of the cornea.
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PMID:Selective blockade of substance P or neurokinin A receptors reduces the expression of c-fos in trigeminal subnucleus caudalis after corneal stimulation in the rat. 946 Jul 60

Immediate early gene (IEG) expression has been routinely used by neuroscientists as an index of neuronal activation. In the case of the hypothalamic-pituitary-adrenal axis, induction of c-fos and/or NGFI-B mRNAs in the parvocellular paraventricular nucleus (pPVN) has been documented after a variety of stimuli that increase adrenocorticotropin (ACTH) in the systemic circulation. However, the functional relationship between expression of IEGs and transcription of the genes for the ACTH secretagogues corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) is not clear. While investigating the neuroendocrine correlates of alcohol administration via different routes (intraperitoneal vs intragastric), we noted a difference in the time course of NGFI-B mRNA expression in the pPVN, despite comparable dynamics in ACTH secretion. By comparing the temporal cascade of transcriptional events in vivo after alcohol injection via either route, we sought to determine functional relationships between IEGs and the induction of CRF and AVP heteronuclear RNAs (hnRNAs). One advantage of our paradigm is the use of the same stimulus (systemic alcohol injection) in which access to the CNS does not differ between the groups to be compared. Intraperitoneal administration of the drug resulted in significant increases in c-fos mRNA, Fos protein, CRF hnRNA, and AVP hnRNA. In contrast, intragastric treatment evoked a brief, modest elevation in c-fos mRNA and Fos protein, increased AVP hnRNA, and caused no detectable change in CRF hnRNA. These data indicate that robust increases in CRF hnRNA are closely linked to full expression of c-fos mRNA and Fos protein. In addition, the expression of NGFI-B after both routes of administration is indicative of cellular activation within the pPVN in parallel with secretion of ACTH.
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PMID:Divergence in the expression of molecular markers of neuronal activation in the parvocellular paraventricular nucleus of the hypothalamus evoked by alcohol administration via different routes. 959 11


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