Functions for pro-opiomelanocortin-derived peptides in obesity and diabetes

2010 ◽  
Vol 428 (3) ◽  
pp. 305-324 ◽  
Author(s):  
Kathleen G. Mountjoy
Keyword(s):  
Reproductive Organs ◽  
Melanocortin Receptor ◽  
Melanocortin Receptors ◽  
Null Mouse ◽  
Receptor Subtypes ◽  
Melanocortin System ◽  
Peripheral Tissues ◽  
Obesity And Diabetes ◽  
Gut Hormone ◽  
Wide Range

Melanocortin peptides, derived from POMC (pro-opiomelanocortin) are produced in the ARH (arcuate nucleus of the hypothalamus) neurons and the neurons in the commissural NTS (nucleus of the solitary tract) of the brainstem, in anterior and intermediate lobes of the pituitary, skin and a wide range of peripheral tissues, including reproductive organs. A hypothetical model for functional roles of melanocortin receptors in maintaining energy balance was proposed in 1997. Since this time, there has been an extraordinary amount of knowledge gained about POMC-derived peptides in relation to energy homoeostasis. Development of a Pomc-null mouse provided definitive proof that POMC-derived peptides are critical for the regulation of energy homoeostasis. The melanocortin system consists of endogenous agonists and antagonists, five melanocortin receptor subtypes and receptor accessory proteins. The melanocortin system, as is now known, is far more complex than most of us could have imagined in 1997, and, similarly, the importance of this system for regulating energy homoeostasis in the general human population is much greater than we would have predicted. Of the known factors that can cause human obesity, or protect against it, the melanocortin system is by far the most significant. The present review is a discussion of the current understanding of the roles and mechanism of action of POMC, melanocortin receptors and AgRP (agouti-related peptide) in obesity and Type 2 diabetes and how the central and/or peripheral melanocortin systems mediate nutrient, leptin, insulin, gut hormone and cytokine regulation of energy homoeostasis.

scholarly journals Expression and signalling characteristics of the corticotrophin-releasing hormone receptors during the implantation phase in the human endometrium

2004 ◽  
Vol 32 (1) ◽  
pp. 21-32 ◽  
Author(s):  
E Karteris ◽  
N Papadopoulou ◽  
DK Grammatopoulos ◽  
EW Hillhouse
Keyword(s):  
Hormone Receptors ◽  
Splice Variants ◽  
Reproductive Organs ◽  
Human Endometrium ◽  
Receptor Subtypes ◽  
Endometrial Stromal Cells ◽  
Peripheral Tissues ◽  
Releasing Hormone ◽  
Receptor Repertoire ◽  
Crh Receptors

Corticotrophin-releasing hormone (CRH) has been identified in several peripheral tissues, including the female reproductive organs. CRH is expressed in the placenta, myometrium, epithelial endometrium and the endometrial stromal cells at all phases of the menstrual cycle. Similarly, CRH receptors are present in pregnant and non-pregnant myometrium, placenta and endometrium. Putative roles of CRH in the endometrium include involvement in implantation, decidualisation and maintenance of pregnancy. In this study we sought to investigate in detail the CRH receptor repertoire expressed in the human endometrium and their signalling characteristics. Using RT-PCR we were able to demonstrate the expression of CRH receptor 1alpha (CRH-R1alpha) and CRH-R2alpha in the human endometrium. CRH-R1beta was present in 40% of endometrial cDNAs examined. No apparent expression of CRH-R2beta, CRH-R2gamma or any other CRH-R1 splice variants was detected. Chemical cross-linking studies with 125I-ovine CRH revealed that the endometrial CRH receptor has a molecular weight of 45 kDa. Using the non-hydrolysable photoreactive analogue [alpha-32P]GTP-azidoanilide and peptide antisera raised against G-protein alpha-subunits, we then studied coupling of endometrial CRH receptors to G proteins. Treatment of endometrial membranes with human CRH (100 nM) increased the labelling of Gq and Gs, but not Gi or Go. These results were supported by experiments in epithelial cells of the non-pregnant human endometrium in the secretory phase which showed that CRH induced increases in both cAMP and inositol trisphosphate levels. These results suggested that CRH may exert multiple effects in the human endometrium via distinct signalling cascades. These events are possibly mediated via different receptor subtypes.

scholarly journals The Melanocortin System in Control of Inflammation

2010 ◽  
Vol 10 ◽  
pp. 1840-1853 ◽  
Author(s):  
Anna Catania ◽  
Caterina Lonati ◽  
Andrea Sordi ◽  
Andrea Carlin ◽  
Patrizia Leonardi ◽  
...  
Keyword(s):  
Receptor Activation ◽  
Brain Regions ◽  
New Drugs ◽  
Melanocortin Receptor ◽  
Receptor Subtypes ◽  
Melanocortin System ◽  
Inflammatory Disorders ◽  
Melanocyte Stimulating Hormone ◽  
Common Precursor ◽  
Anti Inflammatory

Melanocortin peptides, the collective term for α-, β-, and γ-melanocyte-stimulating hormone (α-, β-, γ-MSH) and adrenocorticotropic hormone (ACTH), are elements of an ancient modulatory system. Natural melanocortins derive from the common precursor pro-opiomelanocortin (POMC). Five receptor subtypes for melanocortins (MC1-MC5) are widely distributed in brain regions and in peripheral cells. Melanocortin receptor activation by natural or synthetic ligands exerts marked anti-inflammatory and immunomodulatory effects. The anticytokine action and the inhibitory influences on inflammatory cell migration make melanocortins potential new drugs for treatment of inflammatory disorders. Effectiveness in treatment of acute, chronic, and systemic inflammatory disorders is well documented in preclinical studies. Further, melanocortins are promising compounds in neuroprotection. This review examines the main signaling circuits in anti-inflammatory and immunomodulatory actions of melanocortins, and the potential therapeutic use of these molecules.

scholarly journals Identification of avian alpha-melanocyte-stimulating hormone in the eye: temporal and spatial regulation of expression in the developing chicken

2001 ◽  
Vol 168 (3) ◽  
pp. 527-537 ◽  
Author(s):  
K Teshigawara ◽  
S Takahashi ◽  
T Boswell ◽  
Q Li ◽  
S Tanaka ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Neural Retina ◽  
Melanocortin Receptor ◽  
Receptor Subtypes ◽  
Peripheral Tissues ◽  
Rpe Cells ◽  
Melanocyte Stimulating Hormone ◽  
Cone Cells ◽  
Stimulating Hormone

The presence and possible physiological roles of alpha-melanocyte-stimulating hormone (alpha-MSH) in the peripheral tissues of birds have not been established. By a combination of RT-PCR, immunocytochemistry and in situ hybridization, we have examined alpha-MSH expression in the eye of the chicken during development. In the 1-day-old chick, alpha-MSH was expressed in the retinal pigment epithelial (RPE) cells, and also at a lower level in the cone cells. The melanocortin receptor subtypes, CMC1, CMC4 and CMC5, were expressed in the layers of the choroid and the neural retina, but not in the RPE cells. It is probable that the RPE cells secrete alpha-MSH to exert paracrine effects on the choroid and neural retina. During embryonic development, alpha-MSH immunoreactivity in the RPE cells was initially detected at embryonic day 10, and increased in intensity as development proceeded. No cone cells were stained with anti-alpha-MSH antiserum in any of the embryonic stages tested. The immunoreactivities for two prohormone convertases, PC1 and PC2, were co-localized to the RPE cells with a pattern of staining similar to that of alpha-MSH. Despite containing alpha-MSH immunoreactivity, the RPE cells in 1-day-old chicks expressed no immunoreactivity for the endoproteases. Furthermore, in a 3-day-old chick, pro-opiomelanocortin mRNA was detectable by in situ hybridization only in the photoreceptor layer and not in the RPE cells. These results suggest that the RPE cells and the cone cells are intraocular sources of alpha-MSH in the embryonic and postnatal life of the chicken respectively. Embryonic expression of alpha-MSH in the RPE cells implies a possible role for the peptide in ocular development.

scholarly journals Bombesin receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
Jim Battey ◽  
Richard V. Benya ◽  
Robert T. Jensen ◽  
Terry W. Moody
Keyword(s):  
Physiological Role ◽  
Smooth Muscle Contraction ◽  
Tissue Growth ◽  
Receptor Subtypes ◽  
Neoplastic Tissue ◽  
Peripheral Tissues ◽  
Feeding Regulation ◽  
Wide Range ◽  
Bombesin Receptors ◽  
Stimulation Of

Mammalian bombesin (Bn) receptors comprise 3 subtypes: BB1, BB2, BB3 (nomenclature recommended by the NC-IUPHAR Subcommittee on bombesin receptors, [109]). BB1 and BB2 are activated by the endogenous ligands gastrin-releasing peptide (GRP), neuromedin B (NMB) and GRP-(18-27). bombesin is a tetradecapeptide, originally derived from amphibians. The three Bn receptor subtypes couple primarily to the Gq/11 and G12/13 family of G proteins [109]. Each of these receptors is widely distributed in the CNS and peripheral tissues [73, 109, 236, 265, 226, 348]. Activation of BB1 and BB2 receptors causes a wide range of physiological/pathophysiogical actions, including the stimulation of normal and neoplastic tissue growth, smooth-muscle contraction, feeding behavior, secretion and many central nervous system effects including regulation of circadian rhythm and mediation of pruritus [112, 113, 109, 115, 116, 155, 189, 236]. A physiological role for the BB3 receptor has yet to be fully defined although recently studies suggest an important role in glucose and insulin regulation, metabolic homeostasis, feeding, regulation of body temperature, obesity, diabetes mellitus and growth of normal/neoplastic tissues [73, 157, 203, 332].

scholarly journals Melanocortin System in Kidney Homeostasis and Disease: Novel Therapeutic Opportunities

2021 ◽  
Vol 12 ◽  
Author(s):  
Mingyang Chang ◽  
Bohan Chen ◽  
James Shaffner ◽  
Lance D. Dworkin ◽  
Rujun Gong
Keyword(s):  
Kidney Disease ◽  
Kidney Diseases ◽  
Melanocortin Receptor ◽  
Melanocortin Receptors ◽  
Melanocortin System ◽  
Glomerular Diseases ◽  
Effector Cells ◽  
Potential Strategy ◽  
Hormone System

Melanocortin peptides, melanocortin receptors, melanocortin receptor accessory proteins, and endogenous antagonists of melanocortin receptors are the key components constituting the melanocortin hormone system, one of the most complex and important hormonal systems in our body. A plethora of evidence suggests that melanocortins possess a protective activity in a variety of kidney diseases in both rodent models and human patients. In particular, the steroidogenic melanocortin peptide adrenocorticotropic hormone (ACTH), has been shown to exert a beneficial effect in a number of kidney diseases, possibly via a mechanism independent of its steroidogenic activity. In patients with steroid-resistant nephrotic glomerulopathy, ACTH monotherapy is still effective in inducing proteinuria remission. This has inspired research on potential implications of the melanocortin system in glomerular diseases. However, our understanding of the role of the melanocortinergic pathway in kidney disease is very limited, and there are still huge unknowns to be explored. The most controversial among these is the identification of effector cells in the kidney as well as the melanocortin receptors responsible for conveying the renoprotective action. This review article introduces the melanocortin hormone system, summarizes the existing evidence for the expression of melanocortin receptors in the kidney, and evaluates the potential strategy of melanocortin therapy for kidney disease.

scholarly journals Bombesin receptors in GtoPdb v.2021.2

2021 ◽  
Vol 2021 (2) ◽  
Author(s):  
Jim Battey ◽  
Richard V. Benya ◽  
Robert T. Jensen ◽  
Terry W. Moody
Keyword(s):  
Body Temperature ◽  
Physiological Role ◽  
Smooth Muscle Contraction ◽  
Tissue Growth ◽  
Receptor Subtypes ◽  
Neoplastic Tissue ◽  
Peripheral Tissues ◽  
Feeding Regulation ◽  
Wide Range ◽  
Bombesin Receptors

Mammalian bombesin (Bn) receptors comprise 3 subtypes: BB1, BB2, BB3 (nomenclature recommended by the NC-IUPHAR Subcommittee on bombesin receptors, [115]). BB1 and BB2 are activated by the endogenous ligands neuromedin B (NMB), gastrin-releasing peptide (GRP), and GRP-(18-27). bombesin is a tetra-decapeptide, originally derived from amphibians. The three Bn receptor subtypes couple primarily to the Gq/11 and G12/13 family of G proteins [115]. Each of these receptors is widely distributed in the CNS and peripheral tissues [78, 115, 249, 278, 237, 362]. Activation of BB1 and BB2 receptors causes a wide range of physiological/pathophysiogical actions, including the stimulation of normal and neoplastic tissue growth, smooth-muscle contraction, gastrointestinal motility, feeding behavior, secretion and many central nervous system effects including regulation of circadian rhythm, body temperature control, sighing and mediation of pruritus [149, 202, 244, 115, 196, 249, 306, 68, 34, 332]. A physiological role for the BB3 receptor has yet to be fully defined although recently studies suggest an important role in glucose and insulin regulation, metabolic homeostasis, feeding, regulation of body temperature, obesity, diabetes mellitus and growth of normal/neoplastic tissues [148, 78, 162, 214, 346, 200]. Bn receptors are one of the most frequently overexpressed receptors in cancers and are receiving increased attention for their roles in tumor growth, as well as for tumour imaging and for receptor targeted cytotoxicity [202, 276, 8, 161].

scholarly journals Pharmacological modulation of MRAP2 protein on melanocortin receptors in the sea lamprey

2019 ◽  
Vol 8 (4) ◽  
pp. 378-388 ◽  
Author(s):  
Ming Zhu ◽  
Bingxin Xu ◽  
Meng Wang ◽  
Shangyun Liu ◽  
Yue Zhang ◽  
...  
Keyword(s):  
Surface Expression ◽  
Sea Lamprey ◽  
Melanocortin Receptor ◽  
Regulatory Function ◽  
Carboxyl Terminus ◽  
Melanocortin Receptors ◽  
Melanocortin System ◽  
Pharmacological Modulation ◽  
Primitive Species ◽  
First Time

Melanocortin receptors (MCRs) and their accessory proteins (MRAPs) evolutionarily first appear in the genome of sea lamprey. The most ancient melanocortin system consists of only two melanocortin receptors (slMCa and slMCb) and one MRAP2 (slMRAP2) protein, but the physiological roles have not been fully explored in this primitive species. Here, we synthesize and characterize the pharmacological features of slMRAP2 protein on two slMCRs. Our results show that the slMRAP2 protein lacks the long carboxyl terminus; it directly interacts and decreases the surface expression but enhances the α-MSH-induced agonism of slMCa and slMCb. In comparison with higher organisms such as elephant shark and zebrafish, we also demonstrate the constantly evolving regulatory function of the carboxyl terminus of MRAP2 protein, the unique antiparallel topology of slMRAP2 dimer and the homo- and hetero-dimerization of two slMCRs. This study elucidates the presence and modulation of melanocortin receptor by the accessory protein of the agnathans for the first time, which provides a better insight of the melanocortin system in ancient species of chordates.

scholarly journals Natural Experiment on Trade and Investment Liberalization and Soft Drink Consumption

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
Y Tcholakov
Keyword(s):  
Public Health ◽  
International Trade ◽  
Natural Experiment ◽  
Soft Drink ◽  
Trade Agreement ◽  
P Value ◽  
Soft Drink Consumption ◽  
Obesity And Diabetes ◽  
Wide Range ◽  
The Impact

Abstract Background Globalization is recognized to as a contributing factor to a health harming environment through a variety of mechanisms including through changes in food systems and food availability. Sugar-sweetened beverage (SSB) consumption is linked to obesity and diabetes and its regulation is a key priority for public health. The Comprehensive and Progressive Agreement for Trans-Pacific Partnership (CPTPP) is an international trade agreement between 11 countries. Methods This project uses of natural experiment methods to predict the impact of the entry into force of the CPTPP on SSB consumption. These methods allow quantitative inferences to be drawn in the situations where the exposure is not randomly assigned. Soft drink consumption data was collected from the Euromonitor database for 80 countries from all regions. This data was used to estimate the effect of agreements similar to the TPP. Results Eleven country trade agreement pairs were identified. In 5 cases out of the 11, the exposed country had a higher soft drink consumption at five years after the trade agreement. The effect of the trade agreement exposure for an average country in the sample in a trade agreement was found to be 1.10 (95% CI: 1.01-1.18; p-value: 0.03) after adjusting for GDP and the involvement of the US. In 7 of the 11 member-countries soft drink consumption is expected to increase yielding an average increase of 9.0% in those countries; the changes did not yield statistically significant differences in others. Conclusions This projected extended the use of synthetic methods to the projection of future effects of policy implementation. While it showed that there may be increasing trend of SSB consumption in certain scenarios, this could not be generalized to all cases. This illustrates the wide range of effects of international trade liberalization and highlights that national policy probably plays a strong modulating role on the impact that it has on local food environments. Key messages Globalization can lead to health harming environments and its impacts should further be studied by public health professionals and researchers. Many global policies have the potential to lead to significant health impacts but are negotiated without involving public health experts.

Health Disparities and the Law: Wrongs in Search of a Right

2003 ◽  
Vol 29 (2-3) ◽  
pp. 363-380
Author(s):  
Mary Anne Bobinski
Keyword(s):  
Public Health ◽  
Health Planning ◽  
Healthy People ◽  
Public Action ◽  
Traditional Health ◽  
Obesity And Diabetes ◽  
Wide Range ◽  
State Coercion ◽  
Healthy People 2010 ◽  
Over Time

Healthy People 2010 provides our Nation with the wide range of public health opportunities that exist in the first decade of the 21st century. With 467 objectives in 28 focus areas, Healthy People 2010 will be a tremendously valuable asset … . Healthy People 2010 reflects the very best in public health planning—it is comprehensive, it was created by a broad coalition of experts from many sectors, it has been designed to measure progress over time, and, most important, it clearly lays out a series of objectives to bring better health to all people in this country.The current responses to the traditional health perils … have been weakened. At the same time, it seems to this outsider as though the entire public health establishment is united around the proposition that massive public action should be taken to deal with the new “epidemics,” such as obesity and diabetes … . But the use of the term “epidemic” is just the wrong way to think about this issue. There are no noncommunicable epidemics … . Yet the designation [of] obesity as a public health epidemic is designed to signal that state coercion is appropriate … .

The melanocortin system

2003 ◽  
Vol 284 (3) ◽  
pp. E468-E474 ◽  
Author(s):  
Ira Gantz ◽  
Tung M. Fong
Keyword(s):  
Sexual Function ◽  
Energy Homeostasis ◽  
Melanocortin Receptors ◽  
Experimental Basis ◽  
Melanocortin System ◽  
Genetic Studies ◽  
Melanocortin Peptides ◽  
Selective Agonists ◽  
Made In

The melanocortin system consists of melanocortin peptides derived from the proopiomelanocortin gene, five melanocortin receptors, two endogenous antagonists, and two ancillary proteins. This review provides an abbreviated account of the basic biochemistry, pharmacology, and physiology of the melanocortin system and highlights progress made in four areas. In particular, recent pharmacological and genetic studies have affirmed the role of melanocortins in pigmentation, inflammation, energy homeostasis, and sexual function. Development of selective agonists and antagonists is expected to further facilitate the investigation of these complex physiological functions and provide an experimental basis for new pharmacotherapies.

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