UNIPROT:P01189 - FACTA Search

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)

Evidence from a number of sources indicates that the major site of pro-opiomelanocortin (POMC)-producing cells in the CNS is the arcuate nucleus of the hypothalamus. Using immunocytochemical techniques, a second, smaller group of POMC cells has been detected in the nucleus tractus solitarius (NTS) area of the caudal medulla. However, POMC mRNA has never been reported in the NTS even though it has been found in other extrahypothalamic brain regions. Thus, there is some uncertainty as to whether POMC peptides are actually synthesized de novo in the NTS. In the present study, we used biochemical and anatomical techniques to examine whether POMC mRNA is localized in the NTS. Using in situ hybridization, cells containing POMC mRNA were found in the caudal portion of the NTS. The nucleic acid distribution correlated well with the anatomical distribution of 16k POMC peptide immunoreactivity as determined by immunocytochemistry. Northern analysis revealed that the apparent size of POMC mRNA in the NTS was similar to that found in the arcuate nucleus or the pituitary gland. Results of RNase protection assays using a POMC riboprobe complementary to the 5' end of exon 3 suggested that POMC mRNA in the NTS and arcuate nucleus are identical in this region of the message at least. We also calculated POMC peptide product to mRNA ratios in different tissues and found that NTS cells appear to produce less peptide per mRNA molecule than those in the arcuate nucleus or pituitary gland.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Evidence that beta-endorphin is synthesized in cells in the nucleus tractus solitarius: detection of POMC mRNA. 152 60

Melanin concentrating hormone (MCH) is a key neuroendocrine peptide which is involved in the regulation of body color in teleost fish. Antigenically similar peptides exist in higher vertebrates including rodents and man. The precise function(s) of these peptides in these higher vertebrates has yet to be fully elucidated, although regulatory roles in stress-induced or corticotropin-releasing hormone-stimulated ACTH release and/or water balance have been proposed. The salmon, rat, and human MCH cDNA clones have been isolated and sequenced. We isolated and characterized the structure of the rat MCH gene. In addition to providing the complete nucleotide sequence of this gene, we demonstrate that there is a single copy of this gene in the rat genome. The structure of the rat MCH gene indicates that the MCH mRNA is encoded by three exons. Using primer extension and RNase protection assays, the transcriptional start sites of hypothalamic MCH mRNA were determined, allowing us to define the promoter region of this gene. We also characterize the central nervous system distribution of expression of the MCH gene by Northern blot analysis, demonstrating that the MCH mRNA is found predominantly if not exclusively within the hypothalamus.
...
PMID:Nucleotide sequence and tissue-specific expression of the rat melanin concentrating hormone gene. 226 Oct 81

We have produced and characterized lines of transgenic mice expressing a fusion gene composed of the pituitary expression-specific promoter region of the POMC gene, driving the herpes simplex viral-1 thymidine kinase. Adult mice were treated with the antiherpes agent ganciclovir at 70 mg/kg body weight (ip, twice daily for 10-12 days). Approximately 98% of the pituitary intermediate lobe melanotropes and anterior lobe corticotropes were ablated as determined by immunocytochemistry and RIA specific for the POMC-derived peptides, ACTH, beta-endorophin, and alpha-MSH. The number of lactotropes, somatotropes, thyrotropes, and gonadotropes was not altered compared with controls, indicating that in the adult pituitary, POMC products are not required to maintain the distribution of cell types. As expected, plasma corticosterone levels were substantially decreased after POMC cell ablation. In situ hybridization studies showed that the mouse ACTH receptor was expressed uniformly throughout the adrenal cortex, and RNase protection assays revealed that the ACTH receptor mRNA decreased after pituitary POMC cell ablation. Additionally, RNase protection assays showed that pituitary POMC cell ablation resulted in the decrease of adrenal p450c11 beta transcripts while p450c11AS (aldosterone synthase) mRNA levels remained constant. These data demonstrate differential regulation of steroid pathway-specific enzymes by POMC products. Our results also suggest that the thymidine kinase cell obliteration technique may not be dependent on cell division as a prerequisite for cytotoxicity, thus supporting the idea that targeted molecular ablation using cell- and tissue-specific promoter sequences to drive viral thymidine kinase expression can be refined further to study other nonmitotic cells.
...
PMID:Targeted ablation of pituitary pre-proopiomelanocortin cells by herpes simplex virus-1 thymidine kinase differentially regulates mRNAs encoding the adrenocorticotropin receptor and aldosterone synthase in the mouse adrenal gland. 747 75

The effects of acute and chronic treatments with ethanol and acute treatments with an ethanol metabolite, acetaldehyde, on proopiomelanocortin (POMC) mRNA expression were compared with those of these agents on the secretion of a POMC gene product, beta-endorphin (beta-EP) peptide. The level of POMC mRNA in cultured cells was determined using an RNase protection assay, and the accumulation of immunoreactive beta-EP (IR-beta-EP) peptide in the culture medium was measured by radioimmunoassay. Treatment of hypothalamic cells with 25-, 50-, and 100-mM doses of ethanol or 12.5 and 25 microM acetaldehyde for 3 h increased POMC mRNA levels. The stimulatory effect of ethanol on POMC mRNA levels lasted for a period of 12 h, although the percentage increase of the ethanol-stimulated mRNA level was gradually reduced over time. Acute treatments with ethanol and acetaldehyde also elevated IR-beta-EP secretion from the cultured neurons for a period of 12 h, and the IR-beta-EP secretory response developed desensitization after 24 h of ethanol incubation. The close association between the ethanol-induced IR-beta-EP secretion and ethanol-regulated POMC mRNA expression suggests that ethanol regulates both secretion and production of beta-EP peptide in the hypothalamic neurons.
...
PMID:Comparison of the effects of alcohol and acetaldehyde on proopiomelanocortin mRNA levels and beta-endorphin secretion from hypothalamic neurons in primary cultures. 770 32

Membrane depolarization is a critical element of neuronal signaling. In this study, the biochemical and molecular mechanisms involved in transcriptional regulation of the corticotropin-releasing hormone (CRH) gene by depolarization were investigated. In PC-12 cells, potassium-induced membrane depolarization increased expression of a CRH-reporter construct in a cAMP-dependent manner. This synergistic activation was mediated via calcium influx, predominantly via L-type calcium channels, and calmodulin. RNase protection assays demonstrated increased levels of CRH-reporter transcripts in stably transfected cells after treatment with cAMP and potassium, with the induced transcripts initiating at the major transcription initiation site of the human CRH gene. At the genomic level, the CRH cAMP-responsive element conferred both positive cAMP and synergistic cAMP/depolarization regulation to a heterologous promoter. Additionally, DNase I protection assays demonstrated similar nuclear protein/DNA binding profiles across the cAMP-responsive element after treatment of PC-12 cells with potassium or potassium/cAMP. These results support a model in which the protein(s) binding to the cAMP-responsive element integrates signals initiated by multiple pathways (cAMP and calcium) and transmits that integrated signal to the basal transcription machinery, resulting in increased levels of gene expression.
...
PMID:The cAMP-responsive element in the corticotropin-releasing hormone gene mediates transcriptional regulation by depolarization. 818 84

Several lines of evidence from different laboratories suggest that hypothalamic beta-endorphinergic activity decreases around the time of initiation of the LH surge and may increase on estrus to extinguish the expression of the daily neuronal signal for the surge. In several hormone systems, factors that stimulate or suppress hormone release also stimulate or repress transcription of the hormone gene and translation of the messenger RNA encoding the hormone. Therefore, information about neurohormone activity may be inferred from data on changes in the levels of RNA species encoding these neurohormones. We used a solution hybridization/RNase protection assay to test the hypotheses that 1) the abundance of primary transcript of the hypothalamic POMC gene decreases at the time of initiation of the proestrous LH surge and 2) levels of POMC primary transcript (and by inference, levels of beta-endorphin neuronal activity and secretion) increase on estrus. 96 rats exhibiting at least two consecutive 4-day estrous cycles were killed at either 0600 or 1300 h on proestrus and estrus. Dissections of the medial basal hypothalamus were pooled into 4 samples at each time-point (6 rats per sample) and RNA was extracted from nuclear and cytoplasmic fractions separately. We measured levels of POMC primary transcript, processing intermediate and fully spliced mRNA in the nuclear fractions and POMC mRNA in cytoplasmic fractions. Compared to 0600 h, levels of POMC primary transcript decreased significantly during the afternoons of both proestrus and estrus (P < 0.05). Levels of nuclear processing intermediate RNA and cytoplasmic mRNA followed the same trend but the afternoon declines did not reach statistical significance. We conclude from these data that the afternoon decline in POMC gene expression is not unique to the day of proestrus and we speculate that an afternoon decline in beta-endorphinergic neuronal activity may instead be a component of the daily signal for the LH surge.
...
PMID:The effect of time of day on levels of hypothalamic proopiomelanocortin primary transcript, processing intermediate and messenger ribonucleic acid in proestrous and estrous rats. 829 55

Melanocortins (MC), neuropeptides derived from pro-opiomelanocortin, have been implicated in enhancing neurite outgrowth via an as yet unknown mechanism. Recently, five MC receptors have been identified, three of which, the MC3-R, the MC4-R and the MC5-R, are expressed in the nervous system. In this study, alpha-MSH and the melanocortin analog [D-Phe7]ACTH (4-10) were able to stimulate neurite outgrowth in the neuroblastoma cell line Neuro 2A. ACTH (4-10), gamma2-MSH and ORG2766 were inactive. In addition, the MC4-R antagonist [D-Arg8]ACTH (4-10), inhibited the alpha-MSH effect, indicating that the MC4-R mediated stimulation of neurite outgrowth by alpha-MSH. Indeed, the presence of MC4-R mRNA in Neuro 2A cells was demonstrated by a RNase protection assay. Heterologous expression of the MC5-R in Neuro 2A cells lead to the recruitment of a responsiveness to gamma2-MSH, but did not increase the effect of alpha-MSH on neurite outgrowth. This finding indicated that the function of MC4-R can also be exerted by another MC receptor, suggesting that the coupling to Gs, which they have in common, plays an essential role in the neurite outgrowth promoting effect. This was further substantiated by the fact that forskolin treatment per se induced neurite outgrowth in a similar fashion. These data imply that the neurotrophic properties of alpha-MSH are likely to result from Gs-coupled MC receptor activity in neuronal cells.
...
PMID:Melanocortin receptors mediate alpha-MSH-induced stimulation of neurite outgrowth in neuro 2A cells. 901 63

We investigated the effectiveness of lipopolysaccharide (LPS) and muramyl dipeptide (MDP) administered into the brain to induce anorexia in acutely fasted Wistar rats allowed to refeed. We also assayed for changes in mRNA levels of IL-1 system components, TNF-alpha, TGF-beta1, glycoprotein 130 (gp 130), leptin receptor (OB-R), pro-opiomelanocortin (POMC), neuropeptide Y (NPY), glucocorticoid receptor (GR), and CRF receptor (CRF-R) in selected brain regions. The data show that LPS and MDP induced anorexia differentially during refeeding. LPS-induced anorexia was of a stronger magnitude and duration than that of MDP. RNase protection assays showed that LPS and MDP significantly increased the expression of IL-1beta, IL-1 receptor type I, and TNF-alpha mRNAs in the cerebellum, hippocampus, and hypothalamus; LPS was more potent in all cases. MDP treatment, on the other hand, induced a stronger increase in hypothalamic levels of IL-1 receptor antagonist (IL-1Ra) and TGF-beta1 mRNAs relative to LPS. In addition, competitive RT-PCR analysis showed that LPS induced an eleven-fold increase in IL-1alpha mRNA in the hypothalamus relative to vehicle. These findings suggest that LPS and MDP mediate anorexia through different cytokine mechanisms. A stronger up-regulation of anti-inflammatory cytokines (IL-1Ra and TGF-beta1) mRNA expression by MDP may be involved in the weaker MDP-induced anorexia relative to LPS. No significant changes were observed in the peptide components examined except for an up-regulation in cerebellar gp 130 mRNA and down-regulation of hypothalamic GR mRNA expression in response to LPS or MDP. This study shows that LPS and MDP induce anorexia in fasted rats allowed to refeed, and suggests an important role for endogenous cytokine-cytokine interactions.
...
PMID:Lipopolysaccharide (LPS)- and muramyl dipeptide (MDP)-induced anorexia during refeeding following acute fasting: characterization of brain cytokine and neuropeptide systems mRNAs. 962 98

Considerable evidence suggest that some responses to smoking and nicotine are mediated by forebrain beta-endorphinergic opioid mechanisms. It has also been demonstrated that nicotine stimulates rat tuberoinfundibular dopaminergic activity. Since we have proposed that interactions between mediobasohypothalamic (MBH) dopaminergic and beta-endorphinergic mechanisms have a key role in neuroendocrine integration, we investigated the effects of chronic nicotine treatment and withdrawal on: (1) MBH concentrations of proopiomelanocortin (POMC, precursor for beta-endorphin biosynthesis) mRNA; (2) MBH concentrations of tyrosine hydroxylase (TH, rate limiting enzyme in catecholamine biosynthesis) mRNA; (3) corresponding serum prolacin, corticosterone, luteinizing hormone (LH), and testosterone concentrations. POMC and TH mRNA levels were measured by RNase protection/solution hybridization assay; serum hormone levels were measured by radioimmunoassay. Adult male rats received subcutaneous injections of either nicotine or saline during the dark period of each day on an increasing frequency (1-3 injections/day) and dosage (0.4-0.5 mg nicotine/kg body weight) schedule over 4 weeks. The rats were sacrificed after 4 weeks treatment and at 1, 3, 7, 14 and 21 days withdrawal. Chronic daily nicotine administration induced significant changes in serum corticosterone, serum prolactin, MBH TH mRNA, and MBH POMC mRNA concentrations that tended to persist through day 3 of withdrawal; serum prolactin and MBH POMC mRNA concentrations were suppressed whereas serum corticosterone and MBH TH mRNA concentrations were stimulated. None of the parameters were significantly different from control levels following 7 or more days of withdrawal from nicotine, except for a significant decrease of MBH POMC mRNA concentrations on day 21. Chronic daily nicotine or withdrawal did not significantly alter serum LH or testosterone concentrations. These results suggest that chronic nicotine inhibited POMC gene expression and thus, probably, biosynthesis of beta-endorphin and other opiomelanocortins. We hypothesize that suppression of forebrain beta-endorphin synthesis in response to long-term nicotine exposure produces a chronically opioid deficient condition which may play an important role in maintaining nicotine self-administration and in mediating some changes during the nicotine withdrawal syndrome.
...
PMID:Effects of chronic nicotine treatment and withdrawal on hypothalamic proopiomelanocortin gene expression and neuroendocrine regulation. 969 29

The pro-opiomelanocortin (POMC) gene is expressed in a subset of hypothalamic and hindbrain neurons and in pituitary melanotrophs and corticotrophs. POMC neurons release the potent opioid beta-endorphin and several active melanocortins that control homeostasis and feeding behavior. POMC gene expression in the CNS is believed to be controlled by distinct cis-acting regulatory sequences. To analyze the transcriptional regulation of POMC in neuronal and endocrine cells, we produced transgenic mice carrying POMC27*, a transgene containing the entire 6 kb of the POMC transcriptional unit together with 13 kb of 5' flanking regions and 8 kb of 3' flanking regions. POMC27* was tagged with a heterologous 30 bp oligonucleotide in the third exon. In situ hybridization studies showed an accurate cell-specific pattern of expression of POMC27* in the arcuate nucleus and the pituitary. Hypothalamic mRNA-positive neurons colocalized entirely with beta-endorphin immunoreactivity. No ectopic transgenic expression was detected in the brain. Deletional analyses demonstrated that neuron-specific expression of POMC transgenes required distal 5' sequences localized upstream of the pituitary-responsive proximal cis-acting elements that were identified previously. POMC27* exhibited a spatial and temporal pattern of expression throughout development that exactly paralleled endogenous POMC. RNase protection assays revealed that POMC27* expression mimicked that of POMC in different areas of the CNS and most peripheral organs with no detectable ectopic expression. Hormonal regulation of POMC27* and POMC was identical in the hypothalamus and pituitary. These results show that distal 5' sequences of the POMC gene located between -13 and -2 kb target expression into the CNS of transgenic mice in a precise neuron-specific, developmentally and hormonally regulated manner.
...
PMID:Authentic cell-specific and developmentally regulated expression of pro-opiomelanocortin genomic fragments in hypothalamic and hindbrain neurons of transgenic mice. 971 35

1 2 3 Next >>