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)

The pro-opiomelanocortin (POMC) gene is expressed very early during pituitary development, before expression of the other pituitary hormone genes, growth hormone and prolactin, and before expression of the Pit-1/GHF-1 transcription factor which activates those genes. Thus, analysis of the POMC promoter should provide markers of the early stages of pituitary development at the time when cells are being committed to expression of one or the other pituitary hormone. We have previously localized the rat POMC promoter to a 543-bp 5'-flanking DNA fragment of the gene using transfection and transgenic mice experiments. We have now used mutagenesis and in vitro protein-DNA binding studies to define three domains of the promoter which have distinct and complementary activities. Within these domains which require each other for full activity, at least nine regulatory elements were defined by in vitro footprinting and replacement mutagenesis. Each element appeared equally important for promoter activity, as mutagenesis of any element had similar effect on promoter activity. Most of the elements bound different AtT-20 nuclear proteins in gel mobility shift experiments. Whereas only two elements appeared to be binding sites for the known transcription factors AP-1 and chicken ovalbumin upstream promoter, the seven other elements appeared to bind nuclear proteins with novel properties. Thus, in contrast to the predominant role of Pit-1/GHF-1 in transcription of the growth hormone and prolactin genes, the control of an early pituitary gene, POMC, appears to depend on the synergistic interaction of several regulatory elements which bind different nuclear proteins.
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PMID:Pituitary pro-opiomelanocortin gene expression requires synergistic interactions of several regulatory elements. 204 65

We have previously shown that central administration of beta-endorphin results in a reduction of ornithine decarboxylase activity. Ornithine decarboxylase catalyses the rate-limiting step in the biosynthesis of the polyamines putrescine, spermidine and spermine, thought to modulate nucleic acid synthesis. The present study examines the effects of intracisternal injection of beta-endorphin on brain and liver DNA synthesis in preweanling rats. In six-day-old rats, beta-endorphin (0.75 micrograms/g brain wt) produced approximately a 70% inhibition in brain and liver DNA synthesis 1 h after injection, and values were still subnormal in both tissues 10 h later. Subcutaneous administration of beta-endorphin did not alter liver DNA synthesis. Thus, it is most likely that the suppressed liver DNA synthesis observed in animals given beta-endorphin intracisternally is mediated by central mechanisms. Co-administration of naloxone plus beta-endorphin intracisternally prevented the response, indicating an opioid receptor-mediated phenomenon. Naloxone alone caused small but significant increases in brain and liver DNA synthesis, suggesting a tonic influence on tissue DNA by endogenous opioids in the CNS. Acute inhibition of ornithine decarboxylase activity by alpha-difluoromethylornithine did not alter DNA synthesis, indicating that the decreases in DNA synthesis induced by beta-endorphin are unrelated to the ornithine decarboxylase/polyamine system. The effect appears to be restricted to early development as no significant changes in DNA synthesis were obtained in 20-day-old animals. The results from these studies indicate that CNS beta-endorphin has the ability to influence DNA synthesis in central as well as in peripheral tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of central administration of beta-endorphin on brain and liver DNA synthesis in preweanling rats. 205 54

The region -15 to -3 of the pro-opiomelanocortin (POMC) gene promoter specifically binds a transcription factor previously designated PO-B. This region of the POMC gene is involved in the control of constitutive POMC gene expression since mutation of the PO-B DNA-binding site severely reduces transcription from the POMC promoter both in vivo and in vitro (Riegel, A. T., Remenick, J., Wolford, R., Berard, D., and Hager, G. (1990) Nucleic Acids Res. 18, 4513-4521). We have now purified PO-B from HeLa cells approximately 25,000-fold to greater than 90% homogeneity by a combination of ion exchange and reversed phase chromatography. In addition we have studied post-translational modifications that alter the affinity of purified PO-B for its cognate DNA binding site. In Southwestern analysis of column fractions, two bands of apparent molecular masses of 54 and 56 kDa bound specifically to the PO-B recognition sequence. The two copurified components have indistinguishable amino acid composition, are highly hydrophobic, and are heat and acid stable. DNA-binding specificity studies suggest that PO-B does not represent any previously described transcription factor. In addition, dephosphorylation of both species with acid phosphatase induced an about 30-fold increase in DNA binding but failed to produce any significant change in electrophoretic mobility. We conclude that the purified PO-B species represent products of the same gene and suggest that the in vivo function of PO-B may be regulated by its phosphorylation status.
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PMID:Purification of PO-B, a protein that has increased affinity for the pro-opiomelanocortin gene promoter after dephosphorylation. 206 9

The effect of tumor necrosis factor (TNF) on the hypothalamic-adrenal stress response was determined by infusion of TNF, 0, 2 x 10(5), and 4 x 10(5) U/kg per 24 hours, in parenterally fed male Wistar rats. Following infusions over 1 to 6 days, adrenal weight was increased with increasing dosage of TNF. Tumor necrosis factor at a dosage of 4 x 10(5) U/kg per 24 hours increased the plasma corticotropin level over the same period. In a further series of experiments the metabolic effects of TNF were compared with the effects of corticosterone, the predominant glucocorticoid in the rat. In comparison with controls, rats given corticosterone (75 mg subcutaneously) or TNF (2 x 10(5) U/kg per 24 hours) demonstrated decreased nitrogen balance and diminished carcass nitrogen content over a 6-day period. Tumor necrosis factor alone, however, induced a significant increase in liver nitrogen content and diminished jejunal mucosa DNA and protein levels in comparison with the control and corticosterone groups. Finally, adrenalectomized animals receiving basal corticosterone replacement were infused with TNF. Urinary nitrogen loss was significantly diminished in these animals compared with sham adrenalectomized controls, indicating that an intact adrenal stress response is necessary for the increased nitrogen loss following TNF infusion. Tumor necrosis factor may exert an important regulatory influence on the interorgan substrate flux that occurs during critical illness. The effects of TNF on skeletal muscle proteolysis can be simulated by adrenal glucocorticoid administration. The effects of this cytokine on visceral organs appear to be unique to TNF and cannot be reproduced by the administration of glucocorticoids alone.
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PMID:Are the catabolic effects of tumor necrosis factor mediated by glucocorticoids? 215 19

A fragment of human genomic DNA containing the entire pro-opiomelanocortin (POMC) gene was introduced by transfection into the rat glial cell line C6. Blot analysis using poly(A)-rich RNA from the transformed C6 cells showed several hybridization bands. One band was similar in size (1.2 kb) to the POMC mRNA of human pituitary, while two were larger (2.6 and 2.2 kb) and the fourth smaller (800 bp). S1 nuclease mapping revealed that the POMC transcripts in transformed C6 cells were similar to those in non-pituitary tissues. Immunoreactive ACTH (ir-ACTH) was measurable in both the culture medium and cells. Gel chromatography showed that ir-ACTH in the medium eluted at a position identical to that of so-called big ACTH (approximately 40 kDa) which is found in the plasma of patients with ectopic ACTH syndrome. The human POMC gene could thus be expressed in the non-pituitary rat glial cell line C6, although the transcripts and translation products in C6 cells differ from those in the human pituitary. These results suggest that the transformed C6 cell may be a useful tool for studying the regulation of human POMC gene expression in non-pituitary cells.
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PMID:Expression of the human pro-opiomelanocortin gene introduced into a rat glial cell line. 216 Aug 27

A partially purified fraction of extracted porcine pituitary glands which possesses lipolytic and adrenocorticotropic activity has been characterised. It consists of six adrenocorticotropin(ACTH)-like peptides (five of which have not been previously described) which were each purified by sequential reverse-phase (rp) HPLC. Their complete primary structures were determined following amino acid compositional analysis, extensive peptide mapping and partial sequencing. Four of the fragments represent the following ACTH fragments; ACTH(1-31), ACTH(7-34), ACTH(7-36) and ACTH(7-38). By combined analytical rpHPLC and an ACTH radioimmunoassay (with an antiserum exhibiting full cross-reaction with all six ACTH variants isolated here), evidence was obtained from analysis of extracts of whole pituitary that these fragments of ACTH exist in significant amounts relative to intact ACTH(1-39). This suggests that ACTH can undergo more extensive differential proteolytic processing than previously thought. These peptides were found to possess reduced or a complete absence of ACTH-like biological activity. Therefore the biological significance of this processing needs to be resolved. The other two fragments also resembled fragments of ACTH but each possessed the same, single amino acid substitution: a threonine replacing the arginine at the position corresponding to position 8 in the ACTH sequence and had the structures [Thr8]ACTH(1-31) and [Thr8]ACTH(7-31). They possess little ACTH-like biological activity. If these variants are derived from a variant ACTH, this would be a significant finding in view of the site of the amino acid substitution and the highly conserved nature of the ACTH primary structure. The possible physiological and genetic implications are briefly discussed. In this study attempts were also made to identify the DNA coding for the mutant ACTH sequence.
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PMID:Isolation and full structural characterisation of six adrenocorticotropin-like peptides from porcine pituitary gland. Identification of three novel fragments of adrenocorticotropin and of two forms of a novel adrenocorticotropin-like peptide. 217 74

To characterize the effect of ethanol on the hypothalamic beta-endorphin-containing neurons, rat fetal hypothalamic neurons were maintained in primary culture, and the secretion of beta-endorphin (beta-EP) was determined after ethanol challenges. Constant exposure to ethanol at doses of 6-50 mM produced a dose-dependent increase in basal secretion of beta-EP from these cultured cells. These doses of ethanol did not produce any significant effect on cell viability, DNA or protein content. The stimulated secretion of beta-EP following constant ethanol exposure is short-lasting. However, intermittent ethanol exposures maintained the ethanol stimulatory action on beta-EP secretion for a longer time. The magnitude of the beta-EP response to 50 mM ethanol is similar to that of the beta-EP response to 56 mM of potassium. Ethanol-stimulated beta-EP secretion required extracellular calcium and was blocked by a calcium channel blocker; a sodium channel blocker did not affect ethanol-stimulated secretion. These results suggest that the neuron culture system is a useful model for studying the cellular mechanisms involved in the ethanol-regulated hypothalamic opioid secretion.
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PMID:Effect of acute ethanol on beta-endorphin secretion from rat fetal hypothalamic neurons in primary cultures. 221 79

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.
DNA Cell Biol 1990 Nov
PMID:Nucleotide sequence and tissue-specific expression of the rat melanin concentrating hormone gene. 226 Oct 81

Recent studies of whole brain in rat pups have shown a marked decrease in DNA synthesis following intracisternal (i.c.) administration of beta-endorphin (BE). This investigation examines DNA synthesis in the cerebral cortex and cerebellum to determine whether the effect shows regional selectivity. Two- to twenty-day-old rats were given a single ic injection of BE, and DNA synthesis was assessed 1 h later. In the cerebral cortex, a region that undergoes major phases of cell multiplication in the immediate pre- and postnatal periods, BE significantly decreased DNA synthesis in 2-day-old rats, and a maximal inhibition was obtained by 4 days of age. In contrast, the cerebellum, a region that grows predominantly after birth, showed less sensitivity to BE during the early postnatal days, and a maximal effect was not attained until 10 days of age. While at 15 days of age the inhibition began to diminish in the cortex, a maximal effect was still seen in the cerebellum. Naloxone prevented the response in both brain regions, indicating the participation of opioid receptors. These results indicate that CNS BE is apparently able to alter DNA synthesis throughout the brain, with the greatest sensitivity occurring in those regions with highest mitotic rates at the time of exposure to BE.
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PMID:Effects of beta-endorphin on DNA synthesis in brain regions of preweanling rats. 228 32

Glucocorticoids regulate gene expression by causing the glucocorticoid receptor to bind to an enhancer-like DNA element termed the glucocorticoid regulatory element (GRE). The resultant effect on transcription of specific genes causes a cascade of intracellular events that determines the growth or differentiated function of the target tissue. Although virtually all animal tissues respond to glucocorticoids, it has proven difficult to elucidate the molecular events which underlie physiologically important glucocorticoid effects such as lymphocyte death or poor wound healing. In this paper, a tryptic fragment of the glucocorticoid receptor (17K-GR) is shown to bind selectively to DNA containing a GRE. When a mixture of the mouse mammary tumor virus (MMTV) long terminal repeat (LTR) region and plasmid vector DNA was extracted using the intact glucocorticoid receptor or the 17K-GR, the 17K-GR retained a greater proportion of LTR vs. plasmid DNA. The 17K-GR-LTR complex was also more resistant to salt extraction. Extraction of Bam HI-digested mouse genomic DNA resulted in enrichment of the pro-opiomelanocortin (POMC) gene 5' fragment (which contains a GRE) vs. the 3' fragment which does not. A mouse genomic phage library was enriched for GRE-containing sequences by extraction using the 17K-GR. The frequency of POMC-positive plaques was determined to gauge enrichment of down-regulated genes, and the frequency of phosphoenolpyruvate carboxy-kinase-positive plaques was determined to gauge enrichment of up-regulated genes. The frequencies obtained (1.2 x 10(-3) and 3.5 x 10(-3), respectively) indicated that a family of glucocorticoid-regulated genes totaling approximately 300 had been isolated in a genomic sublibrary.
DNA Cell Biol 1990 Mar
PMID:Isolation of a genomic sublibrary enriched for glucocorticoid-regulated genes. 234 94


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