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Melanocyte Stimulating Hormone (melanocyte + stimulating_hormone)
Selected AbstractsMitigating Photosensitivity of Erythropoietic Protoporphyria Patients by an Agonistic Analog of ,-Melanocyte Stimulating Hormone,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 6 2009Juergen H. Harms Erythropoietic protoporphyria (EPP) is a rare hereditary disorder characterized by dermal accumulation of the photosensitizer protoporphyrin IX. Following sunlight exposure, the resulting photosensitivity is manifested first as pain, later as erythema, edema and dermal lesions. Afamelanotide (Nle4 -d-Phe7 -,-MSH), a synthetic analog of ,-melanocyte stimulating hormone and agonist of the melanocortin-1-receptor, promotes melanin synthesis, increasing skin pigmentation. This study examines the efficacy of afamelanotide in preventing symptoms in patients with EPP. A sustained-release subcutaneous implant of 20 mg afamelanotide was administered twice, with a 60-day interval to five EPP patients. Therapeutic efficacy was assessed by a photoprovocation test using standardized white light irradiation, melanin density (MD) determination and daily recording of sunlight exposure and symptoms. From Day 30 to Day 120 tolerance to photoprovocation significantly increased compared with baseline (P = 0.007) and skin MD was significantly higher than that recorded at baseline (P = 0.004). Except for two low-grade pain episodes, patients recorded no phototoxic events past Day 4 of treatment. Tolerance to natural sunlight was up to 24 times longer than prior to therapy. The findings demonstrate beneficial effects of afamelanotide in patients with EPP. Due to the limited number of patients enrolled and the design being an open-label study, confirmation by a large-scale trial is required. [source] Acetoside inhibits ,-MSH-induced melanin production in B16 melanoma cells by inactivation of adenyl cyclaseJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2009Ho Sun Song Abstract Objectives The aim of the study was to determine the mechanism of the whitening effect of acteoside. Methods We used tyrosinase activity and melanin production stimulated in B16 melanoma cells by ,-melanocyte stimulating hormone (,-MSH) or forskolin to measure the whitening effect of acteoside. Key findings Acteoside did not directly inhibit mushroom tyrosinase activity, but dose-dependently inhibited tyrosinase activity and melanin production in B16 melanoma cells stimulated by 1 ,mol/l ,-MSH. Acteoside also reduced cyclic AMP levels in cells stimulated by 1 ,mol/l ,-MSH, suggesting direct inhibition of adenyl cyclase. Acteoside also inhibited productionofbothmelanin and cyclic AMP in cells stimulated by 1 ,mol/l forskolin, an adenyl cyclase activator. Acteoside showed antioxidant activity in a cell-free DPPH (1-diphenyl-2-picrylhydroazyl) assay and inhibited generation of intracellular reactive oxygen species. Conclusions These results suggest that the whitening activity of acteoside results from inhibition of adenyl cyclase and ,-MSH signalling. [source] Ethanol-Induced Increase of Agouti-Related Protein (AgRP) Immunoreactivity in the Arcuate Nucleus of the Hypothalamus of C57BL/6J, but not 129/SvJ, Inbred MiceALCOHOLISM, Issue 4 2010Inmaculada Cubero Background:, The melanocortin (MC) system is composed of peptides that are cleaved from the polypeptide precursor, pro-opiomelanocortin (POMC). Previous research has shown that MC receptor (MCR) agonists reduce, and MCR antagonists increase, ethanol consumption in rats and mice. Consistently, genetic deletion of the endogenous MCR antagonist, agouti-related protein (AgRP), causes reductions of ethanol-reinforced lever pressing and binge-like ethanol drinking in C57BL/6J mice. Ethanol also has direct effects on the central MC system, as chronic exposure to an ethanol-containing diet causes significant reductions of ,-melanocyte stimulating hormone (,-MSH) immunoreactivity in specific brain regions of Sprague-Dawley rats. Together, these observations suggest that the central MC system modulates neurobiological responses to ethanol. To further characterize the role of the MC system in responses to ethanol, here we compared AgRP and ,-MSH immunoreactivity in response to an acute injection of saline or ethanol between high ethanol drinking C57BL/6J mice and moderate ethanol drinking 129/SvJ mice. Methods:, Mice received an intraperitoneal (i.p.) injection of ethanol (1.5 g/kg or 3.5 g/kg; mixed in 0.9% saline) or an equivolume of 0.9% saline. Two hours after injection, animals were sacrificed and their brains were processed for AgRP and ,-MSH immunoreactivity. Results:, Results indicated that acute ethanol administration triggered a dose-dependent increase in AgRP immunoreactivity in the arcuate (ARC) of C57BL/6J mice, an effect that was not evident in the 129/SvJ strain. Although acute administration of ethanol did not influence ,-MSH immunoreactivity, C57BL/6J mice had significantly greater overall ,-MSH immunoreactivity in the ARC, dorsomedial, and lateral regions of the hypothalamus relative to the 129/SvJ strain. In contrast, C57BL/6J mice displayed significantly lower ,-MSH immunoreactivity in the medial amygdala. Conclusions:, The results show that acute ethanol exposure has direct effects on endogenous AgRP activity in ethanol preferring C57BL/6J mice. It is suggested that ethanol-induced increases in AgRP may be part of a positive feedback system that stimulates excessive binge-like ethanol drinking in C57BL/6J mice. Inherent differences in ,-MSH immunoreactivity may contribute to differences in neurobiological responses to ethanol that are characteristically observed between the C57BL/6J and 129/SvJ inbred strains of mice. [source] Proopiomelanocortin Peptides Are Not Essential for Development of Ethanol-Induced Behavioral SensitizationALCOHOLISM, Issue 7 2009Amanda L. Sharpe Background:, Behavioral sensitization is a result of neuroadaptation to repeated drug administration and is hypothesized to reflect an increased susceptibility to drug abuse. Proopiomelanocortin (POMC) derived peptides including ,-endorphin and ,-melanocyte stimulating hormone have been implicated in development of behavioral sensitization and the reinforcing effects of alcohol and other drugs of abuse. This study used a genetically engineered mouse strain that is deficient for neural POMC to directly determine if any POMC peptides are necessary for the development of ethanol-induced locomotor sensitization. Methods:, Adult female mice deficient for POMC in neurons only (Pomc,/,Tg/Tg, KO) and wildtype (Pomc+/+Tg/Tg, WT) littermates were injected once daily with either saline or ethanol (i.p.) for 12 to 13 days. On ethanol test day (day 13 or 14) all mice from both treatment groups received an i.p. injection of ethanol immediately before a 15-minute analysis of locomotor activity. Blood ethanol concentration (BEC) was measured on ethanol test day immediately following the test session. Baseline locomotor activity was measured for 15 minutes after a saline injection 2 days later in both groups. Results:, There was no significant difference in BEC between genotypes (WT = 2.11 ± 0.06; KO = 2.03 ± 0.08 mg/ml). Both WT and nPOMC-deficient mice treated repeatedly with ethanol demonstrated a significant increase in locomotor activity on test day when compared to repeated saline-treated counterparts. In addition, mice of both genotypes in the repeated saline groups showed a significant locomotor stimulant response to acute ethanol injection. Conclusions:, Central POMC peptides are not required for either the acute locomotor stimulatory effect of ethanol or the development of ethanol-induced locomotor sensitization. While these peptides may modulate other ethanol-associated behaviors, they are not essential for development of behavioral sensitization. [source] Mitigating Photosensitivity of Erythropoietic Protoporphyria Patients by an Agonistic Analog of ,-Melanocyte Stimulating Hormone,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 6 2009Juergen H. Harms Erythropoietic protoporphyria (EPP) is a rare hereditary disorder characterized by dermal accumulation of the photosensitizer protoporphyrin IX. Following sunlight exposure, the resulting photosensitivity is manifested first as pain, later as erythema, edema and dermal lesions. Afamelanotide (Nle4 -d-Phe7 -,-MSH), a synthetic analog of ,-melanocyte stimulating hormone and agonist of the melanocortin-1-receptor, promotes melanin synthesis, increasing skin pigmentation. This study examines the efficacy of afamelanotide in preventing symptoms in patients with EPP. A sustained-release subcutaneous implant of 20 mg afamelanotide was administered twice, with a 60-day interval to five EPP patients. Therapeutic efficacy was assessed by a photoprovocation test using standardized white light irradiation, melanin density (MD) determination and daily recording of sunlight exposure and symptoms. From Day 30 to Day 120 tolerance to photoprovocation significantly increased compared with baseline (P = 0.007) and skin MD was significantly higher than that recorded at baseline (P = 0.004). Except for two low-grade pain episodes, patients recorded no phototoxic events past Day 4 of treatment. Tolerance to natural sunlight was up to 24 times longer than prior to therapy. The findings demonstrate beneficial effects of afamelanotide in patients with EPP. Due to the limited number of patients enrolled and the design being an open-label study, confirmation by a large-scale trial is required. [source] The insertion of a full-length Bos taurus LINE element is responsible for a transcriptional deregulation of the Normande Agouti genePIGMENT CELL & MELANOMA RESEARCH, Issue 4 2006Michael Girardot Summary Mammalian pigmentation is controlled by the concerted action of Tyr, Tyrp1 and Dct producing eumelanin and/or pheomelanin in melanocytes. The ratio of these two pigments is determined by the agonist , -melanocyte stimulating hormone and the antagonist Agouti protein acting on the Mc1r. Here we show that the Agouti gene is over-expressed in Normande breed compared with Prim'Holstein breed. The Normande cattle have a characteristic coat color phenotype with a variable presence of black (eumelanin) hair over a red/brown background. We have found a previously undescribed full-length L1-BT element inserted in the 5,-genomic sequence of the Agouti gene in Normande cattle which promotes the over-expression of alternative transcripts. The variable expression of the alternative transcript directed by the long interspersed nuclear element promoter may be the origin of the brindle coat color pattern of the Normande breed. This new bovine Agouti allele isolated in Normande breed has been named Abr. Finally, as ectopic over-expression of Agouti in Ay mice is responsible for the obesity syndrome, we discuss the possible consequences of Abr for meat and milk production in cattle. [source] Cellular and Hormonal Regulation of Pigmentation in Human Ocular MelanocytesPIGMENT CELL & MELANOMA RESEARCH, Issue 4 2001Linda C. Smith-Thomas The purpose of this study was to examine some of the factors that may be relevant to regulating pigmentation in the human eye, specifically whether choroidal and iridial melanocytes are sensitive to regulation by epithelial and stromal cells and ,-melanocyte stimulating hormone (,-MSH). Human choroidal and iridial melanocytes were established in culture and co-cultured with epithelial cells and stromal cells derived both from skin and from eye in order to determine their influence on choroidal and iridial melanocyte dopa oxidase activity. In all cases, co-culture of melanocytes with either epithelial cells or fibroblasts led to an increase in dopa oxidase activity during 5 days of co-culture. The extent of the increase ranged from 60% (non-significant) to as much as 185% when both fibroblasts and keratinocytes were present. The optimal ratio of fibroblasts to melanocytes was 1:10 (for dermal fibroblasts) or 1:2 (for iridial fibroblasts) and 1:1 for all epithelial cells to melanocytes. Both choroidal (three out of three cultures) and iridial (two out of three cultures) melanocytes showed increases in dopa oxidase activity to ,-MSH when cultured in Green's media but the same cells cultured in MCDB153 were unresponsive to ,-MSH. These in vitro studies suggest that ocular melanocytes have the capacity to be influenced by adjacent epithelial and stromal cells with respect to pigmentation. [source] Central regulation of food intake in the neonatal chickANIMAL SCIENCE JOURNAL, Issue 2 2002Mitsuhiro FURUSE ABSTRACT Regulating food intake is complicated in animals including domestic birds. Just after hatching, neonatal chicks find their food by themselves and they can control food intake, since domestic chicken belongs to the precocial type of avian species. Thus, domestic chickens have relatively well-developed mechanisms of food-intake control at hatching. While many aspects of food-intake regulation in chickens appear similar to that in mammals, there are some responses that are unique to chickens. For instance, some neurotransmitters such as neuropeptide Y (NPY), orexin-A, orexin-B, motilin, melanin-concentrating hormone (MCH), galanin, growth hormone releasing factor (GRF) and ghrelin stimulate feeding in mammals. Only NPY strongly stimulates food intake in birds similar to that observed in mammals; however, both orexins, motilin, MCH and galanin failed to alter food intake of the chick. Moreover, GRF and ghrelin suppressed feeding of chicks. On the other hand, cholecystokinin (CCK), gastrin, glucagon-like peptide-1 (GLP-1), corticotropin-releasing factor (CRF), histamine, ,-melanocyte stimulating hormone (,-MSH), leptin and bombesin are known to suppress feeding in mammals. These responses are similar to those of mammals except for leptin. Therefore, the inhibitory mechanisms for feeding are well conserved in chicks. [source] | |||||||||||||