FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2008367188> ?p ?o ?g. }

• W2008367188 endingPage "151" @default.
• W2008367188 startingPage "134" @default.
• W2008367188 abstract "The melanocortin system is a neuroimmunoendocrine hormone system that constitutes the fulcrum in the homeostatic control of a diverse array of physiological functions, including melanogenesis, inflammation, immunomodulation, adrenocortical steroidogenesis, hemodynamics, natriuresis, energy homeostasis, sexual function, and exocrine secretion. The kidney is a quintessential effector organ of the melanocortin hormone system with melanocortin receptors abundantly expressed by multiple kidney parenchymal cells, including podocytes, mesangial cells, glomerular endothelial cells, and renal tubular cells. Converging evidence unequivocally demonstrates that the melanocortin-based therapy using the melanocortin peptide adrenocorticotropic hormone (ACTH) is prominently effective in inducing remission of steroid-resistant nephrotic syndrome caused by various glomerular diseases, including membranous nephropathy, minimal change disease and focal segmental glomerulosclerosis, suggesting a steroidogenic-independent mechanism. Mechanistically, ACTH and other synthetic melanocortin analogues possess potent proteinuria-reducing and renoprotective activities that could be attributable to direct protection of glomerular cells and systemic immunomodulation. Thus, leveraging melanocortin signaling pathways using ACTH or novel synthetic melanocortin analogues represents a promising and pragmatic therapeutic strategy for glomerular diseases. This review article introduces the biophysiology of the melanocortin hormone system with an emphasis on the kidney as a target organ, discusses the existing data on melanocortin therapy for glomerular diseases, and elucidates the potential mechanisms of action. The melanocortin system is a neuroimmunoendocrine hormone system that constitutes the fulcrum in the homeostatic control of a diverse array of physiological functions, including melanogenesis, inflammation, immunomodulation, adrenocortical steroidogenesis, hemodynamics, natriuresis, energy homeostasis, sexual function, and exocrine secretion. The kidney is a quintessential effector organ of the melanocortin hormone system with melanocortin receptors abundantly expressed by multiple kidney parenchymal cells, including podocytes, mesangial cells, glomerular endothelial cells, and renal tubular cells. Converging evidence unequivocally demonstrates that the melanocortin-based therapy using the melanocortin peptide adrenocorticotropic hormone (ACTH) is prominently effective in inducing remission of steroid-resistant nephrotic syndrome caused by various glomerular diseases, including membranous nephropathy, minimal change disease and focal segmental glomerulosclerosis, suggesting a steroidogenic-independent mechanism. Mechanistically, ACTH and other synthetic melanocortin analogues possess potent proteinuria-reducing and renoprotective activities that could be attributable to direct protection of glomerular cells and systemic immunomodulation. Thus, leveraging melanocortin signaling pathways using ACTH or novel synthetic melanocortin analogues represents a promising and pragmatic therapeutic strategy for glomerular diseases. This review article introduces the biophysiology of the melanocortin hormone system with an emphasis on the kidney as a target organ, discusses the existing data on melanocortin therapy for glomerular diseases, and elucidates the potential mechanisms of action. Clinical Summary•The melanocortin system is a set of hormonal, neuropeptidergic, and immune signaling pathways that play an integral role in the homeostatic control of a diverse array of physiological functions, including inflammation, immunomodulation, and adrenocortical steroidogenesis.•The kidney is a quintessential effector organ of the melanocortin hormone system with melanocortin receptors abundantly expressed by multiple kidney parenchymal cells, including podocytes, mesangial cells, glomerular endothelial cells, and renal tubular epithelial cells.•Converging clinical and experimental evidence suggests that the melanocortin-based therapy using ACTH and other melanocortin analogues confers potent proteinuria-reducing and kidney protective effects in various glomerular diseases possibly through both direct protection of glomerular cells and systemic immunomodulation. •The melanocortin system is a set of hormonal, neuropeptidergic, and immune signaling pathways that play an integral role in the homeostatic control of a diverse array of physiological functions, including inflammation, immunomodulation, and adrenocortical steroidogenesis.•The kidney is a quintessential effector organ of the melanocortin hormone system with melanocortin receptors abundantly expressed by multiple kidney parenchymal cells, including podocytes, mesangial cells, glomerular endothelial cells, and renal tubular epithelial cells.•Converging clinical and experimental evidence suggests that the melanocortin-based therapy using ACTH and other melanocortin analogues confers potent proteinuria-reducing and kidney protective effects in various glomerular diseases possibly through both direct protection of glomerular cells and systemic immunomodulation. Glomerular disease is the third leading cause of end-stage kidney failure in the United States.1Meyers C.M. Geanacopoulos M. Holzman L.B. Salant D.J. Glomerular disease workshop.J Am Soc Nephrol. 2005; 16: 3472-3476Crossref PubMed Scopus (6) Google Scholar Treatment of glomerular disease depends on its cause and type, but it is currently limited largely to the use of blockades of the renin-angiotensin-aldosterone system and immunosuppressants, including glucocorticoids, alkylating agents, calcineurin inhibitors, antimetabolites, and more.2Kher A. Kher V. Immunotherapy in renal diseases.Med Clin North Am. 2012; 96: 545-564Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar, 3Jennette J.C. Falk R.J. Diagnosis and management of glomerular diseases.Med Clin North Am. 1997; 81: 653-677Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar, 4Greenbaum L.A. Benndorf R. Smoyer W.E. Childhood nephrotic syndrome–current and future therapies.Nat Rev Nephrol. 2012; 8: 445-458Crossref PubMed Scopus (88) Google Scholar However, these treatments are of limited utility with unsatisfying therapeutic efficacy. Indeed, although 95% of children5Primary nephrotic syndrome in children: clinical significance of histopathologic variants of minimal change and of diffuse mesangial hypercellularity. A Report of the International Study of Kidney Disease in Children.Kidney Int. 1981; 20: 765-771Crossref PubMed Scopus (299) Google Scholar and 50% to 75% of adults6Colattur S.N. Korbet S.M. Long-term outcome of adult onset idiopathic minimal change disease.Saudi J Kidney Dis Transpl. 2000; 11: 334-344PubMed Google Scholar with minimal change disease (MCD) achieve complete remission of proteinuria after an 8-week course of prednisone therapy, more than 70% of all patients who are initially prednisone responsive go on to experience relapses of the nephrotic syndrome, and almost half of them show frequent relapses or steroid dependence and require further immunosuppression.5Primary nephrotic syndrome in children: clinical significance of histopathologic variants of minimal change and of diffuse mesangial hypercellularity. A Report of the International Study of Kidney Disease in Children.Kidney Int. 1981; 20: 765-771Crossref PubMed Scopus (299) Google Scholar, 6Colattur S.N. Korbet S.M. Long-term outcome of adult onset idiopathic minimal change disease.Saudi J Kidney Dis Transpl. 2000; 11: 334-344PubMed Google Scholar For other glomerular diseases such as idiopathic membranous nephropathy (iMN)7Cattran D.C. Delmore T. Roscoe J. et al.A randomized controlled trial of prednisone in patients with idiopathic membranous nephropathy.N Engl J Med. 1989; 320: 210-215Crossref PubMed Scopus (222) Google Scholar, 8Cameron J.S. Healy M.J. Adu D. The Medical Research Council trial of short-term high-dose alternate day prednisolone in idiopathic membranous nephropathy with nephrotic syndrome in adults. The MRC Glomerulonephritis Working Party.Q J Med. 1990; 74: 133-156PubMed Google Scholar and focal segmental glomerulosclerosis (FSGS),9Pei Y. Cattran D. Delmore T. et al.Evidence suggesting under-treatment in adults with idiopathic focal segmental glomerulosclerosis. Regional Glomerulonephritis Registry Study.Am J Med. 1987; 82: 938-944Abstract Full Text PDF PubMed Scopus (142) Google Scholar initial immunosuppressive treatments usually have much lower response rates than for MCD, and additional immunosupressants are essential to induce remission. In actuality, neither the target cells nor the mechanism of action of these immunosuppressants for glomerular disease has been clearly understood.4Greenbaum L.A. Benndorf R. Smoyer W.E. Childhood nephrotic syndrome–current and future therapies.Nat Rev Nephrol. 2012; 8: 445-458Crossref PubMed Scopus (88) Google Scholar Most of these therapeutic strategies were borrowed from transplant immunosuppressive regimens and thus are believed to be effective in glomerular diseases also via immunosuppression; however, some such as cyclosporine A10Faul C. Donnelly M. Merscher-Gomez S. et al.The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A.Nat Med. 2008; 14: 931-938Crossref PubMed Scopus (770) Google Scholar are found to function, at least in part, through nonimmune mechanisms10Faul C. Donnelly M. Merscher-Gomez S. et al.The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A.Nat Med. 2008; 14: 931-938Crossref PubMed Scopus (770) Google Scholar whereas some others, such as levamisole,11Par A. Levamisole as immunostimulant in the clinical practice.Ther Hung. 1983; 31: 161-171PubMed Google Scholar might be effective via immune stimulatory mechanisms. Furthermore, a considerable number of patients suffer from the complications of overimmunosuppression, including opportunistic infection, neoplasia formation, and growth retardation.2Kher A. Kher V. Immunotherapy in renal diseases.Med Clin North Am. 2012; 96: 545-564Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar, 3Jennette J.C. Falk R.J. Diagnosis and management of glomerular diseases.Med Clin North Am. 1997; 81: 653-677Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar Therefore, it is imperative to develop novel and more effective therapeutic modalities with minor side effects to satisfactorily ameliorate glomerular injury and induce remission of proteinuria in patients with refractory glomerular diseases. Recently, a plethora of evidence suggests that melanocortins possess potent antiproteinuric and renoprotective activities and might serve in this role.12Berg A.L. Arnadottir M. ACTH-induced improvement in the nephrotic syndrome in patients with a variety of diagnoses.Nephrol Dial Transplant. 2004; 19: 1305-1307Crossref PubMed Scopus (72) Google Scholar, 13Berg A.L. Nilsson-Ehle P. Arnadottir M. Beneficial effects of ACTH on the serum lipoprotein profile and glomerular function in patients with membranous nephropathy.Kidney Int. 1999; 56: 1534-1543Crossref PubMed Scopus (90) Google Scholar, 14Bomback A.S. Canetta P.A. Beck Jr., L.H. Avalon R. Radhakrishnan J. Appel G.B. Treatment of resistant glomerular diseases with adrenocorticotropic hormone gel: a prospective trial.Am J Nephrol. 2012; 36: 58-67Crossref PubMed Scopus (66) Google Scholar, 15Bomback A.S. Tumlin J.A. Baranski J.J. et al.Treatment of resistant nephrotic syndrome with adrenocorticotropic hormone (ACTH) gel.Drug Des Devel Ther. 2011; 5: 147-153Crossref PubMed Scopus (82) Google Scholar, 16Ponticelli C. Passerini P. Salvadori M. et al.A randomized pilot trial comparing methylprednisolone plus a cytotoxic agent versus synthetic adrenocorticotropic hormone in idiopathic membranous nephropathy.Am J Kidney Dis. 2006; 47: 233-240Abstract Full Text Full Text PDF PubMed Scopus (154) Google Scholar, 17Gong R. The renaissance of corticotropin therapy in proteinuric nephropathies.Nat Rev Nephrol. 2011; 8: 122-128Crossref PubMed Scopus (77) Google Scholar The melanocortin system is a set of hormonal, neuropeptidergic, and immune signaling pathways that play an integral role in the homeostatic control of a diverse array of physiological functions, including melanogenesis, inflammation, immunomodulation, adrenocortical steroidogenesis, hemodynamics, natriuresis, energy homeostasis, sexual function, and exocrine secretion.17Gong R. The renaissance of corticotropin therapy in proteinuric nephropathies.Nat Rev Nephrol. 2011; 8: 122-128Crossref PubMed Scopus (77) Google Scholar The melanocortin hormone system comprises multiple components, including the 5 guanine protein-coupled melanocortin receptors (MCRs); peptide ligands derived from the proopiomelanocortin preprohormone precursor; and endogenous antagonists, agouti signaling protein, and agouti-related protein (Table 1).18Gantz I. Fong T.M. The melanocortin system.Am J Physiol Endocrinol Metab. 2003; 284: E468-E474PubMed Google Scholar, 19Cone R.D. Studies on the physiological functions of the melanocortin system.Endocr Rev. 2006; 27: 736-749Crossref PubMed Scopus (462) Google ScholarTable 1Components of the Melanocortin Hormone SystemThe Melanocortin SystemLigandsACTH, α-MSH, β-MSH, γ-MSHReceptorsMCRs 1-5 (Class A G-protein-coupled receptors)AntagonistsASIPAgRPAbbreviations: ACTH, adrenocorticotropic hormone; AgRP, agouti-related protein; ASIP, agouti signaling protein; MCR, melanocortin receptor; MSH, melanocyte stimulating hormone. Open table in a new tab Abbreviations: ACTH, adrenocorticotropic hormone; AgRP, agouti-related protein; ASIP, agouti signaling protein; MCR, melanocortin receptor; MSH, melanocyte stimulating hormone. The endogenous agonist ligands of the melanocortin hormone system, also known as melanocortins, are a group of hormonal neuropeptides that include adrenocorticotropic hormone (ACTH) and the different forms of melanocyte-stimulating hormone (MSH). Melanocortin peptides are produced by corticotrophs in the anterior lobe of pituitary gland, constituting 15% to 20% of the cells in the anterior lobe of the pituitary gland.20Hadley M.E. Haskell-Luevano C. The proopiomelanocortin system.Ann N Y Acad Sci. 1999; 885: 1-21Crossref PubMed Scopus (129) Google Scholar Melanocortins are synthesized from the precursor peptide pre-proopiomelanocortin, which is encoded by a single-copy gene on chromosome 2p23.3 that is over 8 kb in length.20Hadley M.E. Haskell-Luevano C. The proopiomelanocortin system.Ann N Y Acad Sci. 1999; 885: 1-21Crossref PubMed Scopus (129) Google Scholar The removal of the signal peptide during translation produces the 267-amino-acid polypeptide proopiomelanocortin (POMC), which undergoes a series of post-translational modifications such as phosphorylation and glycosylation before it is proteolytically cleaved by prohormone convertase (PC) enzymes PC1 and PC2 to yield a chemically and biogenetically related family of polypeptides with varying physiological activities, including endorphin, lipotropins, and melanocortins20Hadley M.E. Haskell-Luevano C. The proopiomelanocortin system.Ann N Y Acad Sci. 1999; 885: 1-21Crossref PubMed Scopus (129) Google Scholar (ACTH and α-, β-, and γ-MSH) (Fig 1A). Plasma melanocortins have a diurnal variation in normal subjects21Papadimitriou A. Priftis K.N. Regulation of the hypothalamic-pituitary-adrenal axis.Neuroimmunomodulation. 2009; 16: 265-271Crossref PubMed Scopus (211) Google Scholar, 22Veldhuis J.D. Iranmanesh A. Johnson M.L. Kuzarrakde G. Amplitude, but not frequency, modulation of adrenocorticotropin secretory bursts gives rise to the nyctohemeral rhythm of the corticotropic axis in man.J Clin Endocrinol Metab. 1990; 71: 452-463Crossref PubMed Scopus (166) Google Scholar and can be induced by physical or psychological stress via hypophysiotropic hormones including corticotropin-releasing hormone and arginine vasopressin secreted by the hypothalamus. Conversely, melanocortin synthesis and release are negatively controlled by slow/intermediate or fast feedbacks by many substances secreted within the hypothalamic-pituitary-adrenal axis. Glucocorticoids (cortisol in human) secreted from the adrenal cortex in response to ACTH stimulation generate a negative feedback.21Papadimitriou A. Priftis K.N. Regulation of the hypothalamic-pituitary-adrenal axis.Neuroimmunomodulation. 2009; 16: 265-271Crossref PubMed Scopus (211) Google Scholar Thus, patients treated with a high dose of synthetic glucocorticoids for a long period are likely to have a very low plasma level of melanocortins and develop a clinical constellation of symptoms that highly mimic the phenotypes of POMC deficiency syndrome, a rare genetic disease, including hyperphagia, central obesity, pale skin, and adrenal insufficiency.23Krude H. Biebermann H. Luck W. et al.Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans.Nat Genet. 1998; 19: 155-157Crossref PubMed Scopus (1407) Google Scholar The melanocortins exert their biological functions by binding to and activating the cognate MCRs with different affinity.24Abdel-Malek Z.A. Melanocortin receptors: their functions and regulation by physiological agonists and antagonists.Cell Mol Life Sci. 2001; 58: 434-441Crossref PubMed Scopus (142) Google Scholar So far, 5 MCRs have been cloned and characterized. All of the 5 MCRs are highly conservative across different species and share many homologs.19Cone R.D. Studies on the physiological functions of the melanocortin system.Endocr Rev. 2006; 27: 736-749Crossref PubMed Scopus (462) Google Scholar, 25Cone R.D. Lu D. Koppula S. et al.The melanocortin receptors: agonists, antagonists, and the hormonal control of pigmentation.Recent Prog Horm Res. 1996; 51 (discussion: 318]): 287-317PubMed Google Scholar The MCRs are all members of the rhodopsin family (class A) of 7-transmembrane guanine protein-coupled receptors, which intracellularly mediate their effects mainly by activating adenylate cyclase, leading to stimulation of the cyclic AMP (cAMP)-dependent cell signaling pathways.24Abdel-Malek Z.A. Melanocortin receptors: their functions and regulation by physiological agonists and antagonists.Cell Mol Life Sci. 2001; 58: 434-441Crossref PubMed Scopus (142) Google Scholar The 5 MCRs have distinct tissue distribution, convey signaling of different melanocortins, and mediate varying biological effects.24Abdel-Malek Z.A. Melanocortin receptors: their functions and regulation by physiological agonists and antagonists.Cell Mol Life Sci. 2001; 58: 434-441Crossref PubMed Scopus (142) Google Scholar MC1 R exhibits high affinity for ACTH and most MSH. It is highly expressed in melanocytes and is the principal MCR in the skin, where it mediates pigmentation as 1 of the major biological functions of most melanocortin peptides.19Cone R.D. Studies on the physiological functions of the melanocortin system.Endocr Rev. 2006; 27: 736-749Crossref PubMed Scopus (462) Google Scholar, 25Cone R.D. Lu D. Koppula S. et al.The melanocortin receptors: agonists, antagonists, and the hormonal control of pigmentation.Recent Prog Horm Res. 1996; 51 (discussion: 318]): 287-317PubMed Google Scholar MC1 R is also widely expressed in other organ systems, including adrenals, lung, lymph nodes, ovary, testis, brain, placenta, spleen, and uterus.19Cone R.D. Studies on the physiological functions of the melanocortin system.Endocr Rev. 2006; 27: 736-749Crossref PubMed Scopus (462) Google Scholar, 25Cone R.D. Lu D. Koppula S. et al.The melanocortin receptors: agonists, antagonists, and the hormonal control of pigmentation.Recent Prog Horm Res. 1996; 51 (discussion: 318]): 287-317PubMed Google Scholar It is also present in vascular endothelial cells and immune-competent cells including leukocytes, dendritic cells, and macrophages, suggesting a role of MC1 R in the regulation of inflammatory reaction and immune response.19Cone R.D. Studies on the physiological functions of the melanocortin system.Endocr Rev. 2006; 27: 736-749Crossref PubMed Scopus (462) Google Scholar, 25Cone R.D. Lu D. Koppula S. et al.The melanocortin receptors: agonists, antagonists, and the hormonal control of pigmentation.Recent Prog Horm Res. 1996; 51 (discussion: 318]): 287-317PubMed Google Scholar Indeed, α-MSH26Doi K. Hu X. Yuen P.S. et al.AP214, an analogue of alpha-melanocyte-stimulating hormone, ameliorates sepsis-induced acute kidney injury and mortality.Kidney Int. 2008; 73: 1266-1274Crossref PubMed Scopus (97) Google Scholar or ACTH27Gong R. Dworkin L.D. Adrenocorticotropin (ACTH) gel suppresses renal tubulointerstitial inflammation and injury by direct stimulation of the melanocortin 1 receptor (MC1R).J Am Soc Nephrol. 2011; 22: 136AGoogle Scholar treatment has been shown to prevent acute and chronic inflammation in animal models of multiple diseases, including acute kidney inflammation27Gong R. Dworkin L.D. Adrenocorticotropin (ACTH) gel suppresses renal tubulointerstitial inflammation and injury by direct stimulation of the melanocortin 1 receptor (MC1R).J Am Soc Nephrol. 2011; 22: 136AGoogle Scholar and injury.26Doi K. Hu X. Yuen P.S. et al.AP214, an analogue of alpha-melanocyte-stimulating hormone, ameliorates sepsis-induced acute kidney injury and mortality.Kidney Int. 2008; 73: 1266-1274Crossref PubMed Scopus (97) Google Scholar, 28Si J. Ge Y. Zhuang S. Chen S. Gong R. Adrenocorticotropic hormone ameliorates acute kidney injury by steroidogenic-dependent and -independent mechanisms.Kidney Int. 2013; 83: 635-646Crossref PubMed Scopus (32) Google Scholar Direct evidence of the important role of MC1 R in inflammation and immunomodulation was recently shown in mice with a nonfunctional MC1 R.29Maaser C. Kannengiesser K. Specht C. et al.Crucial role of the melanocortin receptor MC1R in experimental colitis.Gut. 2006; 55: 1415-1422Crossref PubMed Scopus (60) Google Scholar These mice demonstrated a dramatic exacerbation of experimental inflammation,29Maaser C. Kannengiesser K. Specht C. et al.Crucial role of the melanocortin receptor MC1R in experimental colitis.Gut. 2006; 55: 1415-1422Crossref PubMed Scopus (60) Google Scholar confirming a general anti-inflammatory effect of the MC1 R signaling pathway. MC2 R is the primary and exclusive receptor for ACTH that is expressed mainly in the adrenal gland and binds to ACTH with strong affinity but does not bind to the MSH peptides.19Cone R.D. Studies on the physiological functions of the melanocortin system.Endocr Rev. 2006; 27: 736-749Crossref PubMed Scopus (462) Google Scholar, 25Cone R.D. Lu D. Koppula S. et al.The melanocortin receptors: agonists, antagonists, and the hormonal control of pigmentation.Recent Prog Horm Res. 1996; 51 (discussion: 318]): 287-317PubMed Google Scholar Activation of MC2 R initiates a cascade of events affecting multiple steps in steroidogenesis and growth of adrenal cortex. Of note, although MC2 R is predominantly expressed in adrenal cortex, recent studies indicate that it is also present in some other tissues including adipocytes, where MC2 R mediates stress-induced lipolysis via central ACTH release.19Cone R.D. Studies on the physiological functions of the melanocortin system.Endocr Rev. 2006; 27: 736-749Crossref PubMed Scopus (462) Google Scholar, 25Cone R.D. Lu D. Koppula S. et al.The melanocortin receptors: agonists, antagonists, and the hormonal control of pigmentation.Recent Prog Horm Res. 1996; 51 (discussion: 318]): 287-317PubMed Google Scholar MC3 R and MC4 R regulate energy expenditure.19Cone R.D. Studies on the physiological functions of the melanocortin system.Endocr Rev. 2006; 27: 736-749Crossref PubMed Scopus (462) Google Scholar, 25Cone R.D. Lu D. Koppula S. et al.The melanocortin receptors: agonists, antagonists, and the hormonal control of pigmentation.Recent Prog Horm Res. 1996; 51 (discussion: 318]): 287-317PubMed Google Scholar MC3 R is expressed in the brain, predominantly in the arcuate nucleus in the hypothalamus and limbic system and in a few regions of the brain stem, as well as in the periphery, where it has been found in the placenta and gut tissues; it is also abundantly expressed in the heart and in renal distal tubules and thus has been postulated to regulate hemodynamics, natriuresis, and cardiovascular functions. Indeed, γ-MSH promotes urinary salt excretion via MC3 R in the kidneys.30Humphreys M.H. Cardiovascular and renal actions of melanocyte-stimulating hormone peptides.Curr Opin Nephrol Hypertens. 2007; 16: 32-38Crossref PubMed Scopus (29) Google Scholar Mice either with MC3 R knockout or lacking γ-MSH because of a defect in PC2, when fed a high-salt diet, consistently developed severe hypertension.30Humphreys M.H. Cardiovascular and renal actions of melanocyte-stimulating hormone peptides.Curr Opin Nephrol Hypertens. 2007; 16: 32-38Crossref PubMed Scopus (29) Google Scholar MC4 R is predominately found in the central nervous system, where it is represented in almost every brain region, including the cortex, thalamus, hypothalamus, brain stem, and spinal cord.19Cone R.D. Studies on the physiological functions of the melanocortin system.Endocr Rev. 2006; 27: 736-749Crossref PubMed Scopus (462) Google Scholar, 25Cone R.D. Lu D. Koppula S. et al.The melanocortin receptors: agonists, antagonists, and the hormonal control of pigmentation.Recent Prog Horm Res. 1996; 51 (discussion: 318]): 287-317PubMed Google Scholar MC3 R and MC4 R can both bind to ACTH or α-MSH with high affinity, but evidence suggests that they are not redundant in regulating food intake behavior and energy homeostasis, such as hunger and satiety signaling, because the MC4 R receptor knockout mice manifest hyperphagia, obesity, insulin resistance, and increased linear growth whereas the MC3 R receptor knockout animals are not hyperphagic but are still obese.19Cone R.D. Studies on the physiological functions of the melanocortin system.Endocr Rev. 2006; 27: 736-749Crossref PubMed Scopus (462) Google Scholar, 25Cone R.D. Lu D. Koppula S. et al.The melanocortin receptors: agonists, antagonists, and the hormonal control of pigmentation.Recent Prog Horm Res. 1996; 51 (discussion: 318]): 287-317PubMed Google Scholar In addition, MC3 R has been found to have thermoregulatory and immunomodulatory effects, whereas MC4 R could additionally govern mood effects, control erectile function, and mediate aphrodisiac actions.19Cone R.D. Studies on the physiological functions of the melanocortin system.Endocr Rev. 2006; 27: 736-749Crossref PubMed Scopus (462) Google Scholar, 25Cone R.D. Lu D. Koppula S. et al.The melanocortin receptors: agonists, antagonists, and the hormonal control of pigmentation.Recent Prog Horm Res. 1996; 51 (discussion: 318]): 287-317PubMed Google Scholar MC5 R was the last of the MCR gene family to be discovered by homology screening from genomic DNA in the early 1990s.19Cone R.D. Studies on the physiological functions of the melanocortin system.Endocr Rev. 2006; 27: 736-749Crossref PubMed Scopus (462) Google Scholar, 25Cone R.D. Lu D. Koppula S. et al.The melanocortin receptors: agonists, antagonists, and the hormonal control of pigmentation.Recent Prog Horm Res. 1996; 51 (discussion: 318]): 287-317PubMed Google Scholar High expression levels of MC5 R can be found in exocrine glands in addition to various other organs, including adrenal glands, fat cells, liver, lung, lymph nodes, bone marrow, thymus, mammary glands, testis, ovary, pituitary testis, uterus, esophagus, stomach, duodenum, skin, lung, skeletal muscle, exocrine glands, and kidney.19Cone R.D. Studies on the physiological functions of the melanocortin system.Endocr Rev. 2006; 27: 736-749Crossref PubMed Scopus (462) Google Scholar, 25Cone R.D. Lu D. Koppula S. et al.The melanocortin receptors: agonists, antagonists, and the hormonal control of pigmentation.Recent Prog Horm Res. 1996; 51 (discussion: 318]): 287-317PubMed Google Scholar MC5-R-mediated physiological functions are not well understood. Targeted disruption of the MC5 R gene in mice resulted in a severe defect in water repulsion and thermoregulation because of decreased production of sebaceous lipids.19Cone R.D. Studies on the physiological functions of the melanocortin system.Endocr Rev. 2006; 27: 736-749Crossref PubMed Scopus (462) Google Scholar, 25Cone R.D. Lu D. Koppula S. et al.The melanocortin receptors: agonists, antagonists, and the hormonal control of pigmentation.Recent Prog Horm Res. 1996; 51 (discussion: 318]): 287-317PubMed Google Scholar MC5 R has similar affinity to ACTH and α-MSH and is believed to be responsible for the biological functions such as sebaceous gland secretion, thermoregulation, and immunomodulation.19Cone R.D. Studies on the physiological functions of the melanocortin system.Endocr Rev. 2006; 27: 736-749Crossref PubMed Scopus (462) Google Scholar, 25Cone R.D. Lu D. Koppula S. et al.The melanocortin receptors: agonists, antagonists, and the hormonal control of pigmentation.Recent Prog Horm Res. 1996; 51 (discussion: 318]): 287-317PubMed Google Scholar It has been suggested that MC5 R agonists may perhaps alleviate conditions such as dry eyes and mouth, and MC5 R antagonists might be useful in the treatment of acne. In addition, MC5 R is widely expressed on B and T lymphocytes and might mediate immunomodulatory effects of melanocortin peptides such as α-MSH and ACTH.19Cone R.D. Studies on the physiological functions of the melanocortin system.Endocr Rev. 2006; 27: 736-749Crossref PubMed Scopus (462) Google Scholar, 25Cone R.D. Lu D. Koppula S. et al.The melanocortin receptors: agonists, antagonists, and the hormonal control of pigmentation.Recent Prog Horm Res. 1996; 51 (discussion: 318]): 287-317PubMed Google Scholar Receptor b" @default.
• W2008367188 created "2016-06-24" @default.
• W2008367188 creator A5041867945 @default.
• W2008367188 date "2014-03-01" @default.
• W2008367188 modified "2023-10-16" @default.
• W2008367188 title "Leveraging Melanocortin Pathways to Treat Glomerular Diseases" @default.
• W2008367188 cites W1498791370 @default.
• W2008367188 cites W1519043471 @default.
• W2008367188 cites W1577872659 @default.
• W2008367188 cites W1624229824 @default.
• W2008367188 cites W184779548 @default.
• W2008367188 cites W1964666570 @default.
• W2008367188 cites W1965416288 @default.
• W2008367188 cites W1970322783 @default.
• W2008367188 cites W1972755247 @default.
• W2008367188 cites W1978919889 @default.
• W2008367188 cites W1979975359 @default.
• W2008367188 cites W1981860108 @default.
• W2008367188 cites W1982228553 @default.
• W2008367188 cites W1984940334 @default.
• W2008367188 cites W1986801355 @default.
• W2008367188 cites W1988342604 @default.
• W2008367188 cites W1991564985 @default.
• W2008367188 cites W1992820070 @default.
• W2008367188 cites W1997775090 @default.
• W2008367188 cites W2000908273 @default.
• W2008367188 cites W2001707987 @default.
• W2008367188 cites W2005648142 @default.
• W2008367188 cites W2008258516 @default.
• W2008367188 cites W2008388786 @default.
• W2008367188 cites W2009707997 @default.
• W2008367188 cites W2018999902 @default.
• W2008367188 cites W2020987938 @default.
• W2008367188 cites W2023066962 @default.
• W2008367188 cites W2026530727 @default.
• W2008367188 cites W2028226107 @default.
• W2008367188 cites W2030460848 @default.
• W2008367188 cites W2030924703 @default.
• W2008367188 cites W2032368320 @default.
• W2008367188 cites W2032565269 @default.
• W2008367188 cites W2035062720 @default.
• W2008367188 cites W2037719282 @default.
• W2008367188 cites W2040060591 @default.
• W2008367188 cites W2042323290 @default.
• W2008367188 cites W2044050487 @default.
• W2008367188 cites W2044100552 @default.
• W2008367188 cites W2044472727 @default.
• W2008367188 cites W2047567287 @default.
• W2008367188 cites W2047680032 @default.
• W2008367188 cites W2049670746 @default.
• W2008367188 cites W2051190674 @default.
• W2008367188 cites W2051595057 @default.
• W2008367188 cites W2052831952 @default.
• W2008367188 cites W2053952852 @default.
• W2008367188 cites W2063008609 @default.
• W2008367188 cites W2065292451 @default.
• W2008367188 cites W2069089202 @default.
• W2008367188 cites W2072802709 @default.
• W2008367188 cites W2075235384 @default.
• W2008367188 cites W2077889744 @default.
• W2008367188 cites W2083299002 @default.
• W2008367188 cites W2087761925 @default.
• W2008367188 cites W2088616569 @default.
• W2008367188 cites W2089513529 @default.
• W2008367188 cites W2089590765 @default.
• W2008367188 cites W2095752238 @default.
• W2008367188 cites W2099488003 @default.
• W2008367188 cites W2100990796 @default.
• W2008367188 cites W2104602296 @default.
• W2008367188 cites W2110190860 @default.
• W2008367188 cites W2111822216 @default.
• W2008367188 cites W2120361515 @default.
• W2008367188 cites W2120837287 @default.
• W2008367188 cites W2121502193 @default.
• W2008367188 cites W2121636503 @default.
• W2008367188 cites W2132630384 @default.
• W2008367188 cites W2134995734 @default.
• W2008367188 cites W2140642062 @default.
• W2008367188 cites W2144479843 @default.
• W2008367188 cites W2146965144 @default.
• W2008367188 cites W2147397632 @default.
• W2008367188 cites W2147973326 @default.
• W2008367188 cites W2151098851 @default.
• W2008367188 cites W2151342931 @default.
• W2008367188 cites W2155826224 @default.
• W2008367188 cites W2158602178 @default.
• W2008367188 cites W2161080814 @default.
• W2008367188 cites W2164977232 @default.
• W2008367188 cites W2165099278 @default.
• W2008367188 cites W2167549446 @default.
• W2008367188 cites W2167707357 @default.
• W2008367188 cites W2167727277 @default.
• W2008367188 cites W2169990586 @default.
• W2008367188 cites W2171510995 @default.
• W2008367188 cites W2260911688 @default.
• W2008367188 cites W2330138071 @default.
• W2008367188 cites W2766221641 @default.
• W2008367188 cites W3144014357 @default.

• next