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 effects of corticotropin-releasing hormone (CRH) and dexamethasone on proopiomelanocortin (POMC) mRNA levels in cultured pituitary adenoma cells were studied in 10 patients with Cushing's disease. As a control, POMC mRNA levels in cells from nonadenomatous tissues were examined in four patients. Human POMC mRNA in the cells was analyzed by Northern blot hybridization. Human POMC DNA probe hybridized with only a single size class of RNA (approximately 1,200 nucleotides) from the adenoma and nonadenoma cells of each patient. The size of POMC mRNA did not change through the culture or after incubation with CRH or dexamethasone. CRH increased POMC mRNA levels in these cells in a dose- and time-dependent manner. The minimum concentration of CRH required to elevate POMC mRNA levels in these cells exposed for 15 h was 0.1 nM. The minimum duration of 1 nM CRH treatment required to increase these levels was 3 h under our conditions. Inhibitory effects of 1 and 10 micrograms/dl dexamethasone on ACTH release and POMC mRNA levels in nonadenoma cells were greater than those in adenoma cells. These results suggest the following: (a) that the mRNA in cultured pituitary adenoma cells is qualitatively the same as that in vivo; (b) that responses of mRNA levels to CRH are time- and dose-dependent; and (c) that adenoma cells resist the inhibitory effect of dexamethasone on POMC mRNA levels and ACTH release.
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PMID:Effects of corticotropin-releasing hormone and dexamethasone on proopiomelanocortin messenger RNA level in human corticotroph adenoma cells in vitro. 283 42

The steroid 21-hydroxylase (21-OHase) gene is selectively expressed at high levels in cells of the adrenal cortex and is transcriptionally regulated by corticotropin (ACTH). In this study, we examined the contribution of cis-acting nucleotide sequences to the regulated expression of the mouse 21-OHase gene. The 5'-flanking sequences of the mouse 21-OHase gene, extending 330 bp upstream from the transcription initiation site, were placed in front of the human growth hormone (hGH) reporter gene, and expression of the fusion gene was measured following transient transfection in Y1 mouse adrenocortical tumor cells. The 330 bp of 21-OHase flanking sequence directed both basal and ACTH-stimulated expression of hGH in Y1 adrenocortical cells but did not direct hGH expression in I-10 mouse testicular Leydig cells or in mouse fibroblast L cells. The 21-OHase/hGH fusion gene was poorly expressed in Y1 mutants defective in cAMP-dependent protein kinase activity. These results indicate that sequences necessary for adrenal cell-selective and ACTH-regulated expression of the 21-OHase gene reside within the first 330 bp of 5'-flanking DNA and that constitutive expression of the gene requires the integrity of cAMP-dependent protein kinase. The constitutive expression of hGH in Y1 cells was decreased dramatically (40-fold) when the 21-OHase flanking sequences in front of hGH were shortened to 156 bp from the transcription initiation site and was restored when the upstream sequences of the 21-OHase gene, from -330 to -150, were added back; the sequences from -330 to -150 were equally effective in either the correct or reverse orientation. From these observations, we conclude that an enhancer element is contained within the sequences from -330 to -150 bp upstream of the 21-OHase transcription initiation site.
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PMID:An enhancer element and a functional cyclic AMP-dependent protein kinase are required for expression of adrenocortical 21-hydroxylase. 284 6

The mechanism by which Ca2+ regulates proopiomelanocortin (POMC)-derived peptide secretion and POMC mRNA levels was investigated in primary cultures of porcine intermediate lobe (IL) cells maintained in serum-free medium. POMC gene expression was evaluated by the dot blot hybridization assay with a 32P-labeled DNA probe complementary to the full-length sequence of porcine POMC mRNA. Treatment of IL cells for 24 h with the calmodulin (CAM) antagonists W7 and W13 reduced POMC mRNA levels by a maximum of 50% in a dose-dependent manner (ED50 approximately 10(-8) M). Accumulation of alpha-melanocyte-stimulating hormone (alpha-MSH) in the medium was also depressed by 50% after 8 h of treatment. The role of protein kinase C (PKC) was investigated by depleting the IL cell PKC content with phorbol ester treatment. Phorbol 12-myristate 13-acetate (PMA) at 5 X 10(-8) M induced a rapid translocation of cytoplasmic PKC activity toward the membrane. After 12 h of PMA treatment, PKC activity was undetectable in either the cytoplasmic or the particulate fractions. The same dose of PMA induced a time-dependent decrease in POMC mRNA levels (50% inhibition after 24 h). The same effect was seen with the phorbol ester phorbol 12,13-dibutyrate at 5 X 10(-8) M, whereas the inactive phorbol ester 4 alpha-phorbol at 5 X 10(-8) M was without effect after 24 h of treatment. PMA treatment had a biphasic effect on alpha-MSH secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ca2+ regulates hormone secretion and proopiomelanocortin gene expression in melanotrope cells via the calmodulin and the protein kinase C pathways. 292 1

Beta-endorphin, leu-enkephalin, dalargin and naloxone influences on cell division have been studied in tongue epithelium of white rats. The preparations were administered at a dose of 0.1 ml per 100 g body weight as a 2.10(-9) M solution. Cell division was studied 24 hours after administration. beta-endorphin, leu-enkephalin, dalargin and naloxone caused a 1.5-1.7-fold increase in the number of DNA-synthesizing nuclei, which was accompanied by an adequate rise in mitotic index in experiments with dalargin.
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PMID:[Comparative effect of opioid receptor ligands on cell division in the epithelium of the tongue in white rats]. 295 33

The effects of dopamine on proopiomelanocortin (POMC) gene expression were compared in primary cultures of the anterior and intermediate lobes of the rat pituitary. A single-stranded POMC complementary DNA was used to quantitate POMC messenger RNA levels. Treatment with dopamine (1 microM) for 48 h reduced POMC messenger RNA levels in the intermediate lobe by 77%, but had no effect on POMC gene expression in the anterior lobe. Dopamine D2 receptors were implicated in the response, as bromocriptine (100 nM). reproduced the dopamine inhibition. The responses to dopamine and bromocriptine were antagonized by haloperidol (10 microM). The decrease in POMC messenger RNA levels was dose dependent with ED50 values of about 50 and 0.1 nM for dopamine and bromocriptine, respectively. The accumulation of POMC-derived peptides, beta-endorphin and alpha-melanocyte-stimulating hormone, over 2 days was measured by radioimmunoassay and was shown to parallel the changes in POMC synthesis. The dopamine-induced inhibition of intermediate lobe POMC synthesis was unaffected by isoprenalin (5 microM) and corticotropin-releasing factor (10 nM), although these treatments had stimulatory effects when tested alone. Activating adenylate cyclase with forskolin (1 microM) or treatment with 8-bromocyclic adenosine monophosphate (1 mM) doubled POMC messenger RNA levels, and, when tested against these stimuli, bromocriptine still produced a 30% inhibition of POMC gene expression. These observations suggest that D2 receptor induced inhibition of POMC gene expression is not only mediated by a decrease in cyclic adenosine monophosphate levels. When cells were pretreated with pertussis toxin (100 ng/ml), the bromocriptine-induced inhibition was almost completely lost, suggesting that the dopaminergic inhibition is mediated by guanosine triphosphate binding proteins.
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PMID:Dopamine inhibition of proopiomelanocortin gene expression in the intermediate lobe of the pituitary. Interactions with corticotropin-releasing factor and the beta-adrenergic receptors and the adenylate cyclase system. 296 67

The factors controlling the expression of corticotropin-releasing hormone (CRH), a hypothalamic neuropeptide involved in the regulation of ACTH secretion, are poorly understood partly because a suitable in vitro model is lacking. To study the regulation of CRH gene expression, an 8-kilobase (kb) DNA fragment containing the entire human CRH gene as well as approximately 6 kb of 5' sequence and 0.8 kb of 3' sequence was isolated from a lambda Charon 4A human genomic library and introduced into a mouse anterior pituitary cell line, AtT-20, by CaPO4 transfection with a neomycin-selectable marker. Approximately 10% of the neomycin-resistant lines stably expressed the CRH gene and secreted radioimmunoassay-detectable CRH into culture media at levels greater than 100 pg/ml. By Southern blot analysis the 8-kb DNA fragment containing the CRH gene had been incorporated intact into the AtT-20 genome. In each CRH-producing strain, but not in the parent AtT-20 cell line, we detected by Northern blot analysis an RNA species that hybridized to two radioactive cRNA probes specific for either the 5' or 3' portion of CRH mRNA, and that co-migrated with placental CRH mRNA. Dexamethasone treatment for 24-96 h caused a specific decrease in CRH mRNA and peptide levels of 40-50% in the five CRH-producing cell lines with half-maximal suppression at approximately 10(-9) M dexamethasone, indicating that CRH gene expression is negatively regulated by glucocorticoids. Thus, we have established an in vitro model suitable for studying in detail those cis- and trans-acting factors which regulate CRH gene expression.
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PMID:Expression and dexamethasone regulation of the human corticotropin-releasing hormone gene in a mouse anterior pituitary cell line. 296 6

Recombinant DNA clones corresponding to 11 beta-hydroxylase cytochrome P-450 (P-450(11)beta) have been identified in a bovine adrenocortical cDNA library. These clones, pB11 beta-1 and pB11 beta-2, hybridize to at least three RNA species, 7.2, 6.2, and 4.3 kilobases in length, present in the adrenal cortex. All three RNA species directed cytochrome P-450(11)beta synthesis in an in vitro translation system. Expression of the cytochrome P-450(11)beta gene is tissue specific in that these transcripts were not detected in liver, heart, kidney, or corpus luteum. In cultured bovine adrenocortical cells, adrenocorticotropin (ACTH) or dibutyryl cAMP increased the concentration of cytochrome P-450(11)beta transcripts. This increase appears to be at least partially due to de novo transcription as shown by the action of actinomycin D which effectively blocked the ACTH-induced increase in cytochrome P-450(11)beta RNA level. Furthermore, cycloheximide administered prior to or along with ACTH resulted in the blockage of any new transcription of the cytochrome P-450(11)beta gene as evidenced from the level of RNA. Thus, in addition to potential effects on RNA stabilization, a primary action of ACTH in the regulation of the level of cytochrome P-450(11)beta may be to mediate the induction of an unidentified adrenocortical protein which is required for the activation of cytochrome P-450(11)beta gene expression. These results, together with previous studies (Kramer, R.E., Rainey, W.E., Funkenstein, B., Dee, A., Simpson, E. R., and Waterman, M. R. (1984) J. Biol. Chem. 259, 707-713) that showed increased intracellular levels of cAMP upon treatment of bovine adrenocortical cell cultures with ACTH, suggest a role for cAMP-mediated events in the regulation of cytochrome P-450(11)beta gene expression.
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PMID:Regulation of cytochrome P-45011 beta gene expression by adrenocorticotropin. 298 12

The effects of injections of a synthetic adrenocorticotropin (ACTH 1-17, Synchrodyn) on the rate of DNA labeling in the metaphyseal bone of CD2F1 mice were tested on a chronopharmacological dosing schedule. Groups of mice that had been conditioned to a 12-hr light/12-hr dark schedule were injected at one of six different timepoints, 4 hr apart, during a single 24-hr span with either a low (0.02 I.U./kg) or a high (20 I.U./kg) dose of ACTH 1-17. Control groups received injections of a placebo at corresponding timepoints. Subgroups of mice were injected with [3H]thymidine ([3H]Tdr) to follow the changes in DNA labeling in the proximal tibial metaphysis at 15 min and 2, 4, 8, 12 and 24 hr after ACTH 1-17 or placebo treatment. All mice were injected with the isotope 30 min before killing, except for those killed 15 min after Rx administration where the isotope had been injected 14 min before killing. The data were analyzed both by analysis of variance and by the cosinor method, the latter of which tests the fit of a 24-hr cosine curve to the data. The effect of ACTH 1-17 on the target cell population was dependent not only upon the dose but upon the time of administration. Both doses exerted time-dependent action, ranging from stimulation to inhibition of DNA labeling. Inhibition was noted when the ACTH 1-17 was administered at 2 hr after the beginning of the daily dark span when nocturnal animals become active. When administered at this circadian stage, the larger dose in particular was associated with an inhibition of DNA labeling lasting for 24 hr. The inhibitory effect was much shorter when the same dose was injected 4 hr earlier. Moreover, the large ACTH 1-17 dose had a stimulatory effect lasting for 24 hr when it was administered 2 hr after the onset of the daily light span, with a much shorter stimulation following administration of the large dose at 6 hr after the beginning of the daily dark span. A circadian stage-dependent stimulation or inhibition of DNA labeling at 2 or 14 hr after light onset, respectively, was thus complemented by an initial inhibition followed by stimulation and vice versa at 10 and 18 hr after light onset respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of an adrenocorticotropin analogue, ACTH 1-17, on DNA synthesis in murine metaphyseal bone. 298 40

The mouse pituitary cell line, AtT-20, packages the adrenocorticotropic hormone (ACTH) in secretory vesicles and releases it when the cell is stimulated with secretagogues. These cells have the capacity, after transfection with the appropriate DNA, to package heterologous peptide hormones into the regulated secretory vesicles (Moore, H. P. H., M. D. Walker, F. Lee, and R. B. Kelly, 1983, Cell, 35:531-538). To test if other secreted proteins prefer a different route to the surface, we have transfected AtT-20 cells with DNAs coding for a fragment of a membrane protein, the vesicular stomatitis virus G protein from which the membrane spanning domain has been deleted (Rose, J. K., and J. E. Bergmann, 1982, Cell, 17:813-819). We found that the secreted vesicular stomatitis virus G proteins were not transported to the regulated secretory vesicles. Instead they preferentially exited the cell by the constitutive pathway previously found in these cells (Gumbiner, B., and R. B. Kelly, 1982, Cell, 28:51-59). In contrast, human growth hormone transfected into the cells by the same procedure was transported to the regulated pathway with a similar efficiency as the endogenous hormone ACTH. Transport of the secreted G protein to the regulated pathway, if it occurs at all, is at least 30-fold less efficient than peptide hormones. We conclude that the transport machinery in AtT-20 cells must selectively recognize different secreted proteins and sort them into distinct secretory pathways.
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PMID:Secretory protein targeting in a pituitary cell line: differential transport of foreign secretory proteins to distinct secretory pathways. 299 34

In order to assess the mechanisms of proopiomelanocortin (POMC) gene expression in human ACTH-producing tumors, we performed the simultaneous evaluation of POMC products and messenger RNA (mRNA) in tissue fragments obtained from two corticotropic adenomas, five nonpituitary tumors, and two normal human pituitaries. The POMC products were examined using a combination of gel exclusion chromatography and four different radioimmunoassays directed against gamma 3 melanocyte stimulating hormone (gamma 3MSH), ACTH, gamma-lipotropin (gamma LPH), and beta-endorphin. The POMCmRNA was detected and analyzed by dot and northern blot hybridization using a single-stranded genomic DNA probe corresponding to the coding region of the human POMC gene. Tissue concentrations of POMC products and mRNA showed parallel distributions. Immunoreactive gamma 3MSH and gamma LPH patterns revealed only 16-kD fragment- and gamma LPH-like peptides in normal and tumoral pituitaries; additional gamma 3MSH- and/or beta MSH-like peptides were found in all five nonpituitary tumors. A single POMCmRNA of approximately 1,200 bases (b) was detected in normal and tumoral pituitaries; a single identical POMCmRNA was also found in four nonpituitary tumors. A thymic carcinoid tumor, in addition to the 1,200-b POMCmRNA, contained equal amounts of a second larger POMCmRNA of approximately 1,450 b. It is concluded that POMC gene expression appears qualitatively unaltered in corticotropic adenomas. In nonpituitary tumors, in contrast, abnormal POMC processing is frequent; in addition, an extra POMCmRNA was detected in a thymic tumor with a greater length than the normal mRNA; the mechanisms and pathophysiological implications of these modifications remain to be elucidated.
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PMID:Altered proopiomelanocortin gene expression in adrenocorticotropin-producing nonpituitary tumors. Comparative studies with corticotropic adenomas and normal pituitaries. 299 96


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