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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The yellow obese syndrome in mice encompasses many pleiotropic effects including yellow fur, maturity-onset obesity, hyperinsulinemia, insulin resistance, hyperglycemia, increased skeletal length and lean body mass, and increased susceptibility to neoplasia. The molecular basis of this syndrome is beginning to be unraveled and may have implications for human obesity and diabetes. Normally, the agouti gene is expressed during the hair-growth cycle in the neonatal skin where it functions as a paracrine regulator of pigmentation. The secreted agouti protein antagonizes the binding of the alpha-melanocyte-stimulating hormone to its receptor (melanocortin 1 receptor) on the surface of hair bulb melanocytes, causing alterations in intracellular cAMP levels. Widespread, ectopic expression of the mouse agouti gene is central to the yellow obese phenotype, as demonstrated by the molecular cloning of several dominant agouti mutations and the ubiquitous expression of the wild-type agouti gene in transgenic mice. Recent experiments have revealed that the hypothalamus and adipose tissue are biologically active target sites for agouti in the yellow obese mutant lines.
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PMID:The role of the agouti gene in the yellow obese syndrome. 927 79

The agouti locus influences coat color by antagonizing melanocyte-stimulating hormone (MSH) at its receptor on pigment cells and may antagonize MSH in neural tissue. This study replicates work on rats to assess whether behavioral (neural) effects of the agouti locus are as similar across mammals as those on coat color. Handling, open-field, platform jump, and food-novelty tests were conducted on agouti and nonagouti deer mice (Peromyscus maniculatus) following protocols in C. A. Cottle and E. O. Price (1987). As with rats, nonagouti deer mice were less aggressive, less active, and easier to handle compared with their agouti counterparts. Nonagouti deer mice also groomed more than agouti subjects. Thus, behavioral effects of the agouti locus are conservative, and agouti may be an important modulator of melanocortins in neural as well as integumentary tissue.
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PMID:Effects of the nonagouti coat-color allele on behavior of deer mice (Peromyscus maniculatus): a comparison with Norway rats (Rattus norvegicus). 941 86

In mouse follicular melanocytes, production of eumelanins (brown-black pigments) and pheomelanins (yellow-brownish pigments) is under the control of two intercellular signaling molecules that exert opposite actions, alpha-melanocyte-stimulating hormone (alphaMSH) which preferentially increases the synthesis of eumelanins, and agouti signal protein (ASP) whose expression favors the production of hair containing pheomelanins. In this study, we report that ASP does not only affect mature melanocytes but can also inhibit the differentiation of melanoblasts. We show that both alphaMSH and forskolin promote the differentiation of murine melanoblasts into mature melanocytes and that ASP inhibits this process. We present evidence that the expression of a specific melanogenic transcription factor, microphthalmia, and its binding to an M box regulatory element, is inhibited by ASP. We also show that, in B16 murine melanoma cells, ASP inhibits alphaMSH-stimulated expression of tyrosinase, tyrosine-related proteins 1 and 2 through an inhibition of the transcription activity of their respective promoters. Further, ASP inhibits alphaMSH-induced expression of the microphthalmia gene and reduces the level of microphthalmia in the cells. Our data demonstrate that ASP can regulate both melanoblast differentiation and melanogenesis, pointing out the key role of microphthalmia in the control of these processes.
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PMID:Involvement of microphthalmia in the inhibition of melanocyte lineage differentiation and of melanogenesis by agouti signal protein. 967 80

The action two genetic loci--agouti and the melanocortin receptor-1 (Mc1r)-- have opposing effects in the control of mammalian pigmentation and ultimately determine the color of the pigment produced. In a recent paper, Ollmann et al. confirmed that the agouti protein acts via the Mc1r. They show that high-affinity binding of the agouti protein to Mc1r expressed in mammalian cells can be inhibited by the receptor's natural ligand, alpha-melanocyte-stimulating hormone (alpha-MSH). In addition, genetic studies using mice carrying mutations at the Mc1r and agouti loci on a sensitized background of low tyrosinase expression confirm that a functional Mc1r is required for the maximum pigmentary effect of agouti. Thus, the Mc1r appears to be a unique, bifunctionally controlled receptor, activated by alpha-MSH and antagonized by agouti, both of which contribute to the variability seen in mammalian coat color.
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PMID:Melanocortin receptors and antagonists regulate pigmentation and body weight. 978 Aug 33

Neuropeptide Y (NPY) and the endogenous melanocortin receptor antagonist, agouti gene-related protein (AGRP), coexist in the arcuate nucleus, and both exert orexigenic effects. The present study aimed primarily at determining the brain distribution of AGRP. AGRP mRNA-expressing cells were limited to the arcuate nucleus, representing a major subpopulation (95%) of the NPY neurons, which also was confirmed with immunohistochemistry. AGRP-immunoreactive (-ir) terminals all contained NPY and were observed in many brain regions extending from the rostral telencephalon to the pons, including the parabrachial nucleus. NPY-positive, AGRP-negative terminals were observed in many areas. AGRP-ir terminals were reduced dramatically in all brain regions of mice treated neonatally with monosodium glutamate as well as of mice homozygous for the anorexia mutation. Terminals immunoreactive for the melanocortin peptide alpha-melanocyte-stimulating hormone formed a population separate from, but parallel to, the AGRP-ir terminals. Our results show that arcuate NPY neurons, identified by the presence of AGRP, project more extensively in the brain than previously known and indicate that the feeding regulatory actions of NPY may extend beyond the hypothalamus.
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PMID:The neuropeptide Y/agouti gene-related protein (AGRP) brain circuitry in normal, anorectic, and monosodium glutamate-treated mice. 984 12

Because of ectopic overproduction of agouti protein, yellow alleles (A(y) and A(vy)) of the murine agouti gene may secondarily modulate the synthesis, maturation (i.e., acetylation), and/or tissue deployment of alpha-Melanocyte Stimulating Hormone (MSH). We used HPLC to test the hypothesis that A(y)/a mice exhibit altered concentrations of desacetyl-, monoacetyl-, and diacetyl-alpha-MSH in pituitaries, sera, and telogen hair bulbs when compared to black (a/a) mice. We also used RIA to measure total MSH in those same tissues of A(y)a,a/a, and white-bellied agouti (A(wJ)/A(wJ)) mice (Strain C57BL/6J). We found no evidence that A(y)/a mice possessed an imbalance of des-, mono-, and diacetylated alpha-MSH species. However, radioimmunoassay (RIA) analyses of total MSH suggest that wild-type agouti mice (A(wJ)/A(wJ)) exhibited significantly decreased (P < 0.05) tissue levels of total alpha-MSH in pituitaries, sera, and regenerating hair bulbs when compared to those of mutant A(y)/a and a/a mice.
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PMID:Agouti-related maturation and tissue distribution of alpha-Melanocyte Stimulating Hormone in wild-type (AwJ/AwJ) and mutant (Ay/a,a/a) mice. 987 2

This is a semi-autobiographical coverage of my research career in pigment cell biology presented in the context of the emergence and growth of the discipline. This anecdotal presentation tells about some historical personages in the field. My undergraduate studies at the University of Rochester are related to my graduate work at the University of Iowa. I tell how my dissertation research was derived from a marriage between my interests in experimental embryology and the new field of comparative endocrinology. My early years of research at Iowa and as a young faculty member in Zoology at the University of Arizona were much concerned with the evolution of our knowledge of the chemistry and biology of melanocyte-stimulating hormone (MSH), especially concerning the pigment cells of lower vertebrates. Our developmental, structural, functional, and biochemical characterization of vertebrate chromatophores is described, as is our elucidation of the dermal chromatophore unit. The direct effects of light on changes in pigmentation are considered in descriptions of both the tail-darkening reaction and the role of the pineal gland in melanophore control. Emphasis is placed on the developmental biology of pigmentation, especially on the concept that all pigment cells are derived in common from a stem cell of neural-crest origin, whose expression is influenced by factors, such as melanization-inhibiting factor (MIF), localized in specific areas of the skin to thus produce specific pigmentation patterns. This research is considered in light of what is known about the agouti locus and MSH in the expression of mammalian pigmentation patterns. Part of my work has included ecological considerations, and some of this is touched upon. My role as founder of the journal 'Pigment Cell Research', is presented briefly, as is my involvement in the XIIIth International Pigment Cell Conference and in the establishment of both the International Pigment Cell Society and the International Federation of Pigment Cell Societies. Finally, I comment on the future of research in pigmentation.
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PMID:The emergence of pigment cell biology: a personal view. 1019 81

Desacetyl-alpha-MSH is more abundant than alpha-MSH in the brain, the fetus, human blood, and amniotic fluid, but there is little information on its ability to interact with melanocortin receptors. The aim of this study is to compare and contrast the ability of desacetyl-alpha-MSH and alpha-MSH to couple melanocortin receptors stably expressed in HEK293 cells, to the protein kinase A (PKA) signaling pathway. Desacetyl-alpha-MSH activated mouse MC1, MC3, MC4 and MC5 receptors with EC50s = 0.13, 0.96, 0.53, and 0.84 nM, and alpha-MSH activated these receptors with EC50s = 0.17, 0.88, 1.05, and 1.34 nM, respectively. Mouse agouti protein competitively antagonized alpha-MSH and desacetyl-alpha-MSH coupling to the MC1-R similarly. In contrast, mouse agouti protein antagonized desacetyl-alpha-MSH much more effectively and potently than alpha-MSH coupling the MC4-R to the PKA signaling pathway. Furthermore, mouse agouti protein (10 nM) significantly reduced (1.4-fold) the maximum response of mMC4-R to desacetyl-alpha-MSH and 100 nM mouse agouti significantly increased (4.8-fold) the EC50. Minimal antagonism of alpha-MSH coupling mMC4-R to the PKA signaling pathway was observed with 10 nM mouse agouti, whereas both 50 and 100 nM mouse agouti appeared to reduce the maximum reponse (1.1- and 1.3-fold, respectively) and increase the EC50 (2.5- and 3.4-fold respectively). Mouse agouti protein did not significantly antagonize either alpha-MSH or desacetyl-alpha-MSH coupling mouse MC3 and MC5 receptors. Understanding the similarities and differences in activation of melanocortin receptors by desacetyl-alpha-MSH and alpha-MSH will contribute to delineating the functional roles for these endogenous melanocortin peptides.
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PMID:Agouti antagonism of melanocortin-4 receptor: greater effect with desacetyl-alpha-melanocyte-stimulating hormone (MSH) than with alpha-MSH. 1021 68

The mechanism underlying the leptin-induced increased sympathetic nerve activity and cardiovascular tone was investigated in normal rats. The melanocortin (MC) peptides and other fragments derived from proopiomelancortin (POMC) have a diverse array of biological activities and have been implicated in mediating the feeding behavioral responses to leptin. In this study we evaluated the possible involvement of two major products of POMC, alpha-melanocyte stimulating hormone (alpha-MSH) and beta-endorphin, in mediating the effects of leptin on sympathetic activity and mean arterial pressure (MAP) in normal rats. Intraventricular (i.c.v.) cannulas were implanted in normal rats and allowed to recover. On the day of the study the animals were anesthetized with urethane alpha-chloralose and instrumented for the recording of MAP, lumbar sympathetic nerve activity (LSNA), and heart rate (HR). To determine the correlation between the leptin response and the POMC products, alpha-MSH and beta-endorphins were also injected into the lateral ventricle. alpha-MSH acted to increase MAP and LSNA while beta-endorphin decreased these parameters. Leptin administration by i.c.v. cannula increased the MAP and LSNA in normal rats. The i.c.v. administration of agouti protein, an alpha-MSH receptor antagonist, prior to leptin infusion blocked this response. Likewise, pretreatment with naloxone a beta-endorphin receptor antagonist also blocked the response to leptin. From these studies we conclude that the acute increased LSNA and MAP in response to i.c.v. leptin may be mediated by increased POMC and its subsequent production of breakdown product alpha-MSH and/or beta-endorphin and it is the subsequent action of alpha-MSH that increases MAP and LSNA by activation of the MC4 receptor. The naloxone antagonism of the leptin response is likely due to the blockade of presynaptic opioid inhibition of the MC4 receptor-mediated pressor response.
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PMID:Leptin-induced increase in sympathetic nervous and cardiovascular tone is mediated by proopiomelanocortin (POMC) products. 1056 84

The paraventricular hypothalamic nucleus (PVH) serves as integrator and link between the neuroendocrine and autonomic nervous systems. Neuropeptide-Y (NPY)-producing neurons in the arcuate nucleus project to the PVH, where neurons expressing NPY Y1 receptor (Y1R) have been demonstrated. This projection has been suggested to be involved in the regulation of parameters related to energy metabolism, e.g. food intake and thermoregulation. The present study aimed at characterizing this pathway and chemically defining Y1R-expressing neurons by means of immunohistochemistry. The densely distributed NPY-immunoreactive (ir) terminals in the PVH co-stained for agouti gene-related protein (AGRP) mainly in the medial parvocellular regions, indicating an origin in the arcuate nucleus. This was in contrast to noradrenergic/adrenergic terminals in the PVH, which were less frequently seen to contain NPY-like immunoreactivity. Furthermore, AGRP-ir terminals were seen forming abundant close appositions on Y1R-ir cell bodies. Double staining revealed co-existence of Y1R-like immunoreactivity and immunoreactivities for thyrotropin-releasing hormone (TRH) and, to a minor extent, cocaine- and amphetamine-regulated transcript peptide in parvocellular neurons. No Y1R-like immunoreactivity was noted in parvocellular neurons expressing corticotropin-releasing hormone or in magnocellular neurons expressing vasopressin or oxytocin. The present results suggest that the arcuatoparaventricular NPY projection targets the TRH neurons preferentially via the Y1R, whereas the NPYergic regulation of corticotropinergic and magnocellular neurons may be relayed through other subtypes of NPY receptors. This study further defines the link between NPY-induced feeding and the hypothalamus-pituitary-thyroid axis.
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PMID:Neuropeptide Y innervation and neuropeptide-Y-Y1-receptor-expressing neurons in the paraventricular hypothalamic nucleus of the mouse. 1056 55


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