Proopiomelanocortin and the Immune‐Neuroendocrine Connection

Blalock, J. Edwin

doi:10.1111/j.1749-6632.1999.tb08673.x

Cited by 82 publications

(52 citation statements)

References 62 publications

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“…Recently, Lyons and Blalock (32) detected the full-length POMC mRNA in immune cells by rapid amplification of cDNA ends-PCR. The researchers suggested that the apparent differences from previous results may be due to differences in PCR techniques, primer extension, and/or ribonuclease (18). Furthermore, they reported that in nonstimulated mononuclear cells the amount of full-length POMC mRNA is low, but that mitogenic stimulation enhanced the abundance of this mRNA (32).…”

Section: Discussionmentioning

confidence: 93%

“…The inactive pro-PC2 is bound to 7B2 (a chaperonelike binding protein) and is transported from the ER to later compartments of the secretory pathway, where it matures to active PC2 (16); thereafter, PC2 converts ␤LPH into ␤-MSH and END (17). The subsequent secretion of END requires secretory granules deriving from the Golgi network for transport to the cell membrane (18). In this study we examine whether the components of this classical secretory pathway are also present and functional within inflammatory cells.…”

Section: U Nder Inflammatory Conditions Variousmentioning

confidence: 99%

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Subcellular Pathways of β-Endorphin Synthesis, Processing, and Release from Immunocytes in Inflammatory Pain

et al. 2004

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The opioid peptide beta-endorphin (END) as well as mRNA for its precursor proopiomelanocortin (POMC) are found not only in the pituitary gland, but also within various types of immune cells infiltrating inflamed sc tissue. During stressful stimuli END is released and interacts with peripheral opioid receptors to inhibit pain. However, the subcellular pathways of POMC processing and END release have not yet been delineated in inflammatory cells. The aim of the present study was to examine the presence of POMC, carboxypeptidase E, the prohormone convertases 1 (PC1), and 2 (PC2), PC2-binding protein 7B2, and the release of END from inflammatory cells in rats. Using immunohistochemistry we detected END and POMC alone or colocalized with PC1, PC2, carboxypeptidase E, and 7B2 in macrophages/monocytes, granulocytes, and lymphocytes of the blood and within inflamed sc paw tissue. Immunoelectron microscopy revealed that END is localized within secretory granules packed in membranous structures in macrophages, monocytes, granulocytes, and lymphocytes. Finally, END is released by noradrenaline from immune cells in vitro. Taken together, our results indicate that immune cells express the entire machinery required for POMC processing into functionally active peptides such as END and are able to release these peptides from secretory granules.

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Section: Discussionmentioning

confidence: 93%

Section: U Nder Inflammatory Conditions Variousmentioning

confidence: 99%

Subcellular Pathways of β-Endorphin Synthesis, Processing, and Release from Immunocytes in Inflammatory Pain

et al. 2004

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“…␣-MSH is secreted from hypothalamic neuron terminals (47) and crosses the BBB (48,49), but is also expressed in many peripheral tissues in rodents (50) and humans (51), where it may have various functions, such as modulation of inflammation (52)(53)(54). Because peripheral tissues may contribute significantly to circulating ␣-MSH (50,(52)(53)(54)(55)(56)(57)(58)(59), serum ␣-MSH levels may not accurately reflect hypothalamic ␣-MSH expression in humans.…”

Section: Discussionmentioning

confidence: 94%

Circulating Melanin-Concentrating Hormone, Agouti-Related Protein, and α-Melanocyte-Stimulating Hormone Levels in Relation to Body Composition: Alterations in Response to Food Deprivation and Recombinant Human Leptin Administration

Gavrila

Chan

Miller

et al. 2005

The Journal of Clinical Endocrinology & Metabolism

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We evaluated whether circulating levels of melanin-concentrating hormone (MCH), agouti-related protein (AGRP), and alpha-MSH could serve as useful markers of energy homeostasis in humans. We first assessed correlations of serum MCH, AGRP, and alpha-MSH with anthropometric, dietary, and hormonal variables in a cross-sectional study of 108 healthy humans. We then performed interventional studies to evaluate the effects of fasting and/or leptin administration. In eight healthy, normal weight men, we measured serum MCH, AGRP, and alpha-MSH levels at baseline, after 2 d of fasting alone (a low leptin state), and after 2 d of fasting with replacement dose recombinant methionyl human leptin (r-metHuLeptin) administration to normalize circulating leptin levels. In a separate group of five lean and five obese men, we measured MCH levels in response to increasing circulating leptin levels to the pharmacological range by administration of one r-metHuLeptin dose in the fed state. In the cross-sectional study, serum MCH levels were independently and positively associated with body mass index and fat mass and were higher in women than in men. Furthermore, in our interventional studies, fasting for 2 d significantly decreased leptin levels and increased serum MCH levels. Administration of replacement dose r-metHuLeptin during fasting prevented the fasting-induced increase in MCH levels, but administration of a pharmacological r-metHuLeptin dose in the fed state did not further alter MCH levels. Serum AGRP levels tended to change in directions similar to MCH, but this change was less pronounced and needs to be investigated in larger studies. In contrast, serum alpha-MSH levels did not correlate with body composition parameters, were not associated with caloric or macronutrient intake, and were not significantly affected by fasting or r-metHuLeptin administration. These findings suggest that serum MCH and possibly AGRP levels could serve as useful peripheral markers of changes in energy homeostasis and thus merit additional investigation.

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“…2), and was also lower in the HYPOX than NIL rats (P <0.001)(Campos-Rodriguez, Quintanar-Stephano et al 2006).The fact that HYPOX induced a more marked decrease in the humoral immune responses to outer membrane proteins of Salmonella typhimurium than NIL suggests that the hormones melanocyte stimulating hormone (MSH), AVP, and oxytocin from the neurointermediate pituitary lobe may affect adaptive immune responses. The direct antiinflammatory effects of MSH on immunocytes have been described previously (Catania and Lipton 1993;Blalock 1999;Luger, Scholzen et al 2003;Taylor 2003 Finally, intestinal elimination of Salmonella typhimurium HYPOX and NIL rats was similar to that seen in sham-operated animals. However, it is known that HYPOX animals develop an increased susceptibility to intraperitoneal Salmonella typhimurium infection, and that GH and PRL treatments protect the rats against the disease (Edwards, Yunger et al 1991;Edwards, Ghiasuddin et al 1992).…”

mentioning

confidence: 80%