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 investigated the regulatory influence of several cytokines on the expression of preproenkephalin (PPE) mRNA in human peripheral blood mononuclear cells (PBMC). By use of a quantitative reverse-transcriptase-polymerase chain reaction (RT-PCR), we demonstrate that the T helper 2 cytokines IL-4 and IL-10 are more potent in upregulating PPE mRNA expression in human PBMC than the T helper 1 cytokines IL-2 and gamma-IFN. In addition, TGF-beta is also an effective inducer of PPE mRNA. TGF-beta, IL-4 and IL-10 increase the cytoplasmatic concentration of met-enkephalin in PBMC. Secretion of met-enkephalin in the culture supernatant of IL-4- or IL-10-stimulated PBMC could not be observed, but proenkephalin A-derived met-enkephalin containing peptides could be demonstrated. IL-4 and IL-10 do not induce PPE mRNA via the same pathways. We could observe that PKA is involved in IL-4 mediated PPE mRNA induction, whereas IL-10 apparently uses another route.
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PMID:T helper 2 cytokines induce preproenkephalin mRNA expression and proenkephalin A in human peripheral blood mononuclear cells. 935 52

Recently, overlapping molecular phenotypes of hematopoietic and neuropoietic cells were described in mice. Here, we examined primary human CD34(+) hematopoietic stem and progenitor cells applying specialized cDNA arrays, real-time reverse-transcriptase-polymerase chain reaction (RT-PCR), and fluorescent-activated cell sorter (FACS) analysis focusing on genes involved in neurobiologic functions. We found expression of vesicle fusion and motility genes, ligand- and voltage-gated ion channels, receptor kinases and phosphatases, and, most interestingly, mRNA as well as protein expression of G protein-coupled receptors of neuromediators (corticotropin-releasing hormone 1 [CRH 1] and CRH 2 receptors, orexin/hypocretin 1 and 2 receptors, GABAB receptor, adenosine A(2)B receptor, opioid kappa 1 and mu 1 receptors, and 5-HT 1F receptor). As shown by 2-color immunofluorescence, the protein expression of these receptors was higher in the more immature CD38(dim) than in the CD38(bright) subset within the CD34(+) population, and completely absent in fully differentiated blood cells, suggesting that those receptors play a role in developmentally early CD34(+) stem and progenitor cells. The intracellular concentration of cyclic adenosine monophosphate (cAMP) in CD34(+) cells was diminished significantly upon stimulation of either CRH or orexin receptors, indicating that those are functionally active and coupled to inhibitory G proteins in human hematopoietic cells. In conclusion, these findings suggest a molecular interrelation of neuronal and hematopoietic signaling mechanisms in humans.
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PMID:Primary human CD34+ hematopoietic stem and progenitor cells express functionally active receptors of neuromediators. 1501 51

We report that mice with a targeted null mutation in the interferon type I receptor (IFN-RI), which cannot respond to such IFNs as IFNalpha and IFNbeta, have a 30% reduction in time spent in spontaneous rapid eye movement sleep (REMS) as a consequence of a reduced number of REMS episodes. Time spent in nonrapid eye movement sleep (NREMS) was essentially unaltered in IFN-RI knockouts (KOs) compared to 129 SvEv controls. Body temperature and locomotor activity were similar in both strains of mice. Hypothalamic expression of mRNAs for molecules previously linked to sleep-wake regulation and an IFN-inducible antiviral gene, 2',5'-oligoadenylate synthetase 1a (OAS), were determined by real-time reverse-transcriptase polymerase chain reaction (RT2-PCR). The level of hypocretin A mRNA was elevated in IFN-RI KO mice compared to 129 SvEv mice, while prolactin mRNA and OAS mRNA levels were suppressed. Vasoactive intestinal peptide (VIP) and corticotropin-releasing hormone (CRH) mRNA levels were unchanged relative to controls. Serum prolactin levels were similar in both strains. Results are consistent with the hypothesis that increased hypocretin and reduced prolactin in the hypothalamus of IFN-RI KO mice are responsible for their reduced REMS. In addition, the reduced OAS expression may result in modulation of prolactin receptor signaling and thus contribute to suppression of REMS.
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PMID:Mice deficient in the interferon type I receptor have reduced REM sleep and altered hypothalamic hypocretin, prolactin and 2',5'-oligoadenylate synthetase expression. 1549 63

Urocortin (Ucn) 2 is a new member of the corticotrophin-releasing hormone (CRH) neuropeptide family that is expressed in the central nervous system and peripheral tissues. However, the expression levels of Ucn 2 in various tissues of the rat remains unclear. Thus, the aim of the present study was to characterise the expression of Ucn 2 in the various tissues of the rat. Reverse transcriptase-polymerase chain reaction analysis demonstrated that Ucn 2 mRNA is expressed in the hypothalamus, pituitary, adrenal, stomach, skin, ovary, uterus and skeletal muscle. Histologically, Ucn 2 mRNA and Ucn 2-like immunoreactivity (LI) were demonstrated in both the anterior and intermediate lobes of the pituitary, but not detected in the posterior lobe. Furthermore, all Ucn 2-positive cells in the anterior and intermediate lobes were also positive for beta-endorphin. Ucn 2 mRNA was detected in the adrenal cortex and medulla although Ucn 2-LI was only found in the adrenal medulla. High-performance liquid chromatography analysis of hypothalamic, pituitary, and adrenal extracts showed that the main Ucn 2-LI peak occurred at the same molecular size as that of synthetic Ucn 2. These results suggest that Ucn 2 is synthesised in various tissues, including the anterior and intermediate lobes of the pituitary and the adrenal.
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PMID:Distribution of urocortin 2 in various tissues of the rat. 1615 78

Human mast cells have been shown to release histamine in response to the neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH), but it is unknown whether these cells express proopiomelanocortin (POMC) or POMC-derived peptides. We therefore examined highly purified human skin mast cells and a leukemic mast cell line-1 (HMC-1) for their ability to express POMC and members of the prohormone convertase (PC) family known to process POMC. Furthermore, we investigated whether these cells store and secrete alpha-MSH. Reverse transcriptase-PCR (RT-PCR) analysis revealed that both skin mast cells and HMC-1 cells express POMC mRNA and protein. Expression of the POMC gene at the RNA level in HMC-1 cells could be confirmed by Northern blotting. Transcripts for both PC1 and furin convertase were detectable in skin-derived mast cells and HMC-1 cells, as shown by RT-PCR. In contrast, PC2 transcripts were detected only in skin mast cells, whereas transcripts for paired basic amino acid converting enzyme 4 (PACE4) were present only in HMC-1 cells. Radioimmunoassays performed on cell lysates and cell culture supernatants from human skin-derived mast cells disclosed immunoreactive amounts of alpha-MSH in both fractions. Stimulation with an anti-IgE antibody significantly reduced intracellular alpha-MSH and increased extracellular levels, indicating IgE-mediated secretion of this neuropeptide. Our findings show that human mast cells are active players in the cutaneous POMC system. Mast cell-derived alpha-MSH may contribute to cutaneous hyperpigmentation as seen in patients with urticaria pigmentosa. Moreover, IgE-dependent release of alpha-MSH suggests an immunomodulatory role of this neurohormone during inflammatory and allergic reactions of the skin.
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PMID:Human mast cells in the neurohormonal network: expression of POMC, detection of precursor proteases, and evidence for IgE-dependent secretion of alpha-MSH. 1691 90

It has been suggested that corticotropin-releasing hormone (CRH) receptors CRH-R1 and CRH-R2 might be involved in the modulation of uterine activity during pregnancy. The authors determine the localization, concentrations, and variants of CRH-R1 and CRH-R2 in the human pregnant myometrium from patients undergoing labor and patients not undergoing labor. Biopsies were taken from 40 patients undergoing either elective or emergency cesarean delivery after spontaneous labor. The localization of CRH-R1 and CRH-R2 was examined by immunohistochemistry. The mRNA and protein levels of CRH-R1 and CRH-R2 were measured by quantitative reverse-transcriptase polymerase chain reaction (PCR) and Western blot analysis, respectively. The variants of CRH-R1 and CRH-R2 were determined by PCR analysis followed by sequencing. Both CRH-R1 and CRH-R2 were found by immunohistochemistry to be expressed by smooth muscle cells in the pregnant myometrium. There was no significant difference in mRNA and protein levels of CRH-R1 and CRH-R2 in myometria between the labor and nonlabor groups. Levels of CRH-R1 alpha , R1 beta, R1c, R1e, R1f, and R2 alpha were identified in the pregnant myometrium, and levels of CRH-R1 alpha, R1c, and R2 alpha were detected in both the term labor and nonlabor myometrium. A heterogeneous distribution of other CRH-R1 variants in term labor and nonlabor myometrium was observed. Human myometrium expresses both CRH-R1 and CRH-R2 during pregnancy. A heterogeneous distribution of CRH-R1 variants in term labor and nonlabor myometrium might be related to the effects of CRH on contractile phenotype of myometrium at the term.
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PMID:Expression of corticotropin-releasing hormone receptor type 1 and type 2 in human pregnant myometrium. 1795 85

As gestation progresses, human fetal adrenals (HFA) initiate the production of cortisol, which increases placental corticotropin-releasing hormone (CRH) biosynthesis. While adrenocorticotrophic hormone (ACTH) is important for the onset of cortisol production, the late gestational surge in cortisol production occurs despite falling ACTH levels in the fetal circulation. The authors determine if CRH directly regulates the expression of the ACTH receptor (ACTHR) in HFA definitive/transitional zone (DZ/TZ) cells. DZ/TZ cells isolated from midgestation HFA were cultured before treatment with 0.01 nM to 100 nM CRH or ACTH. Cortisol was measured by radioimmunoassay. Real-time reverse-transcriptase polymerase chain reaction was used to measure ACTHR mRNA. Whole-cell ACTH binding studies were performed using I(125) (Tyr-23) ACTH. CRH produced a dose-dependent rise in cortisol production and caused a time-dependent increase in ACTHR mRNA levels between 12 and 24 hours. As little as 0.1 nM CRH induced ACTHR transcript by 12-fold at 24 hours. Together with ACTH 0.01 nM, 0.03 or 0.1 nM CRH increased ACTHR expression more than ACTH alone. Binding assays demonstrated a 3.5-fold increase in ACTHR protein at 48 hours with combined CRH and ACTH treatment. Physiologic levels of CRH seen in the late-gestation fetus stimulate DZ/TZ ACTHR expression. Since placental CRH production increases strikingly near the end of gestation, the authors suggest that CRH-induced ACTH receptor expression may increase TZ responsiveness to circulating ACTH and contribute to the late gestational rise in cortisol secretion by the HFA, participating in an endocrine cascade that is involved in fetal organ maturation and potentially in the timing of human parturition.
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PMID:The regulation of adrenocorticotrophic hormone receptor by corticotropin-releasing hormone in human fetal adrenal definitive/transitional zone cells. 1795 86

In a previous study, we showed that corticotropin-releasing factor (CRF) is the major thyroid-stimulating hormone (TSH)-releasing factor in the bullfrog (Rana catesbeiana) hypothalamus. Our findings prompted us to ascertain whether CRF or arginine vasotocin (AVT), a known adrenocorticotropic hormone (ACTH) secretagogue in several vertebrates, is the main stimulator of the release of ACTH from the bullfrog pituitary. Both the frog CRF and AVT stimulated the release of immunoassayable ACTH from dispersed anterior pituitary cells in vitro in a concentration-dependent manner. AVT, however, exhibited far more potent ACTH-releasing activity than CRF. Although CRF by itself weakly stimulated ACTH release, it acted synergistically with AVT to enhance the release of ACTH markedly. Mesotocin and AVT-related peptides such as hydrin 1 and hydrin 2 showed relatively weak ACTH-releasing activity. Subsequently, cDNAs encoding the bullfrog AVT V1a-type and V1b-type receptors were molecularly cloned. Reverse transcriptase-PCR using specific primers revealed that the anterior lobe of the pituitary predominantly expressed AVT V1b-type receptor mRNA but scarcely expressed AVT V1a-type receptor mRNA. Abundant signals for V1b-type receptor mRNA in the corticotropes were also detected by in situ hybridization. The results obtained by the experiments with the bullfrog pituitary indicate that AVT acts as the main ACTH-releasing factor through the AVT V1b-type receptor and that CRF acts synergistically with AVT to enhance the release of ACTH.
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PMID:Arginine vasotocin is the major adrenocorticotropic hormone-releasing factor in the bullfrog Rana catesbeiana. 2757 59