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)

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)
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PMID:Evidence that beta-endorphin is synthesized in cells in the nucleus tractus solitarius: detection of POMC mRNA. 152 60

Human fetal adrenal growth after midgestation is very rapid and appears to be dependent upon pituitary adrenocorticotropin (ACTH) in vivo. We hypothesized that the regulation of fetal adrenal growth by ACTH is mediated by ACTH-stimulated local growth factor production. As we have found basic fibroblast growth factor (bFGF) to be a potent mitogen for human fetal adrenal cells in culture, we conducted studies to determine whether bFGF is synthesized by the human fetal adrenal gland and whether bFGF gene expression in primary cultures of human fetal adrenal cells is regulated by ACTH. Bioassayable bFGF-like activity was detected in extracts of whole human fetal adrenal glands and primary cultures of human fetal adrenal cells. Northern blot analysis of total RNA from whole human fetal adrenal glands revealed a characteristic 7-kilobase bFGF mRNA, indicating that the fetal adrenal bFGF bioactivity was most likely due to local synthesis. Slot blot and ribonuclease protection analysis showed that bFGF mRNA was present in very low amounts in total RNA from primary cultures of unstimulated human fetal adrenal cells but was increased 2- to 3-fold in cells exposed to 10 nM ACTH-(1-24) or 1 mM 8-bromoadenosine 3',5'-cyclic monophosphate for 24 hr. bFGF mRNA was localized to adrenocortical cells and not fibroblasts by in situ hybridization. bFGF mRNA was barely detectable in unstimulated cells, whereas it was markedly increased in cells exposed to either ACTH or 8-bromoadenosine 3',5'-cyclic monophosphate. These data support our hypothesis that the regulation of human fetal adrenal growth by ACTH at midgestation may be mediated by the stimulation of local growth factor production, and we suggest that bFGF may play a major role in this process.
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PMID:Basic fibroblast growth factor expression is regulated by corticotropin in the human fetal adrenal: a model for adrenal growth regulation. 171 Dec 31

The silent corticotroph-cell adenoma (SCCA) is characterized by the presence of immunoreactive adrenocorticotropic hormone (ACTH) in the tumor tissue in patients without symptoms of Cushing's disease. To elucidate the pathophysiology of SCCA, the expression of pro-opiomelanocortin (a ACTH precursor) genes was studied in a patient with SCCA and in three patients with Cushing's disease. Pro-opiomelanocortin messenger ribonucleic acid (mRNA) was found in the SCCA tissue to a greater degree than in the adenomas of the patients with Cushing's disease. Northern blot analysis revealed that the size of pro-opiomelanocortin mRNA present in the SCCA tissue was indistinguishable from that in the adenomas associated with Cushing's disease. A ribonuclease mapping study indicated that there were no point mutations in the coding sequence of pro-opiomelanocortin mRNA present in the SCCA tissue. Because of the presence of pro-opiomelanocortin mRNA and immunoreactive ACTH in the adenoma tissue, it is proposed that translation of the mRNA and subsequent accumulation of ACTH precursor occurred in the SCCA. Thus, the absence of Cushing's disease symptoms in this SCCA could not be caused by abnormality in the coding sequence of the pro-opiomelanocortin gene or in ribonucleic acid processing. The occurrence of abnormality at or after the translational steps was strongly suggested.
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PMID:Pro-opiomelanocortin gene expression in silent corticotroph-cell adenoma and Cushing's disease. 215 97

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.
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PMID:Nucleotide sequence and tissue-specific expression of the rat melanin concentrating hormone gene. 226 Oct 81

The insulin-like growth factors (IGFs) may be important autocrine and paracrine mediators of organ growth. We used solution-hybridization/ribonuclease protection assays to examine IGF-I and IGF-II mRNA abundance during hypertrophy or the rat adrenal gland induced by unilateral adrenalectomy or by adrenocorticotropic hormone (ACTH) infusion. Adrenal IGF-I mRNA did not change during the period of rapid organ growth at 18 or 66 h after unilateral adrenalectomy. ACTH infusion induced a time- and dose-dependent decrease in adrenal IGF-I mRNA despite significant increases in gland size. IGF-II mRNA also remained unchanged after unilateral adrenalectomy and decreased after ACTH infusion, to a greater extent than IGF-I mRNA. Liver IGF-I mRNA did not change with ACTH exposure, indicating an effect specific to the adrenal. We also measured adrenal P450scc mRNA as a marker of steroidogenic capacity. P450scc mRNA was unchanged after unilateral adrenalectomy and increased with ACTH infusion. Thus IGF-I and IGF-II mRNAs respond in parallel, but in different fashions with different stimuli for adrenal growth. The decrease in IGF mRNA after exposure to ACTH may be a factor in the ACTH-induced inhibition of compensatory hypertrophy after unilateral adrenalectomy.
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PMID:Rat insulin-like growth factor-I and -II mRNAs are unchanged during compensatory adrenal growth but decrease during ACTH-induced adrenal growth. 226 16

This report presents a technique for recovery of mouse forebrain proteins from two-dimensional sodium dodecyl sulfate-polyacrylamide gels for subsequent primary structure determination. Proteins were visualized by Coomassie staining or salt precipitation and manually cut out of the gel. Excised spots were minced and loaded into an empty precolumn of a reversed-phase high-performance liquid chromatography system. Purified protein was extruded from a gel matrix by pressurized liquid, then separated from gel contaminants by reversed-phase gradient elution, and finally collected in siliconized tubes or on polybrene-coated filter disks for gas-phase sequencing. Several mouse and rat forebrain proteins were purified by this method and sequenced. Three previously unidentified mouse brain proteins with molecular weights of 4,000, 12,000, and 18,500 were partially sequenced and three hemoglobin fragments were structurally identified and mapped. Ribonuclease A, myoglobin, adrenocorticotropin, and bovine somatotropin were also subjected to two-dimensional (2-D) analysis and partially sequenced. Recovery values of 27-95% were obtained for extruded 14C-labeled ribonuclease, carbonic anhydrase, and bovine serum albumin out of sodium dodecyl sulfate-polyacrylamide gel electrophoretic gels. Losses resulting from the multiple handling steps of a 2-D gel separation process were also investigated. Recoveries of 12-17%, as determined by sequencing signals, were achieved. These latter recovery values reflect overall losses incurred in gel-focusing, gel-sizing, staining, destaining, high-pressure liquid extrusion, and N-terminal blockage. This work demonstrates that an array of protein spots can be systematically identified or defined by partial sequencing after high-pressure liquid extrusion from a 2-D gel matrix.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Isolation and sequence analysis of proteins from mouse forebrain using two-dimensional gel electrophoresis coupled to high-pressure liquid extrusion. 281 64

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.
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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.
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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

The melanocortin (MC) peptides mediate a diverse spectrum of biological activities in both the central nervous system and peripheral tissues by interacting with specific guanine nucleotide binding (G protein)-coupled receptors. Previously, four human melanocortin receptor subtypes have been cloned and characterized. In this study, we have isolated mouse complementary DNA (cDNA) and human genomic clones encoding a fifth melanocortin receptor subtype, MC5. Melanocortin peptide stimulation of human MC5, transiently expressed in COS1 cells, results in activation of adenylate cyclase with the following rank order of potency: [Nle4, D-Phe7]-alpha-MSH (melanocyte stimulating hormone) > ACTH (1-24) (adrenocorticotropic hormone) > alpha-MSH > beta-MSH > gamma-MSH. Northern blot hybridization, ribonuclease protection, and reverse transcription/polymerase chain reaction assays indicate that mouse MC5 mRNA is most abundant in skeletal muscle and brain. Lower but detectable levels of MC5 mRNA are also found in RT2-2 retinal neuronal cells, lung, testis, spleen, heart, kidney, and liver.
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PMID:Cloning, expression, and tissue distribution of a fifth melanocortin receptor subtype. 773 52

Gene expression in mammalian cells can be suppressed by oligonucleotides complementary to the target mRNA. This strategy was explored as a means of arresting translation of the prohormone precursor proopiomelanocortin (POMC), used as a model system of peptide messengers that are synthesized and released from endocrine and neuronal cells. The synthesis of the POMC-derived peptides adrenocorticotropin (ACTH) and beta-endorphin (beta-END) was markedly reduced by an oligodeoxynucleotide (ODN) complementary to a region of beta-END mRNA in AtT-20 cells, which retain many of the differentiated phenotypes of corticotrophs; this treatment did not affect the steady-state levels of POMC mRNA. Antisense ODN was stable in cell culture medium for 24 h, and cellular uptake was low (approximately 2.5% of the added ODN); however, the intracellular levels of the ODN were sufficient to form a ribonuclease-resistant duplex with complementary cellular mRNA. Addition of ODN to the cell culture did not affect the cellular levels of chromogranin A-(264-314)/pancreastatin or cell viability and proliferation, as evidenced by bromodeoxyuridine incorporation and ornithine decarboxylase activity. Microinfusion of the antisense ODN in the rat hypothalamic arcuate nucleus, where the majority of POMC-positive brain perikarya are located, significantly reduced ACTH- and beta-END-immunopositive neurons, and antisense ODN-treated rats showed substantially less of the grooming behavior usually observed in a novel environment.
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PMID:Inhibition of proopiomelanocortin expression by an oligodeoxynucleotide complementary to beta-endorphin mRNA. 805 59


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