Regulation of Body Weight by Proopiomelanocortin Peptides in Humans: Lessons from the Nelson Syndrome

Field: Medicine (Health Sciences)

Letters2 August 2005Regulation of Body Weight by Proopiomelanocortin Peptides in Humans: Lessons from the Nelson SyndromeRajagopal V. Sekhar, MD, J. Clay Goodman, MD, Ashok Balasubramanyam, MD, Jeffrey B. Tatro, PhD, and Emese Mihaly, PhDRajagopal V. Sekhar, MDFrom Baylor College of Medicine, Houston, TX 77030; Tufts University School of Medicine, Boston, MA 02111; and Semmelwies University Medical School, 1088 Budapest, Hungary.Search for more papers by this author, J. Clay Goodman, MDFrom Baylor College of Medicine, Houston, TX 77030; Tufts University School of Medicine, Boston, MA 02111; and Semmelwies University Medical School, 1088 Budapest, Hungary.Search for more papers by this author, Ashok Balasubramanyam, MDFrom Baylor College of Medicine, Houston, TX 77030; Tufts University School of Medicine, Boston, MA 02111; and Semmelwies University Medical School, 1088 Budapest, Hungary.Search for more papers by this author, Jeffrey B. Tatro, PhDFrom Baylor College of Medicine, Houston, TX 77030; Tufts University School of Medicine, Boston, MA 02111; and Semmelwies University Medical School, 1088 Budapest, Hungary.Search for more papers by this author, and Emese Mihaly, PhDFrom Baylor College of Medicine, Houston, TX 77030; Tufts University School of Medicine, Boston, MA 02111; and Semmelwies University Medical School, 1088 Budapest, Hungary.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-143-3-200508020-00021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Background: Melanocortins (α-melanocyte-stimulating hormone [MSH] and adrenocorticotropic hormone [ACTH]), in addition to their melanocyte-stimulating actions, may regulate energy balance through hypothalamic melanocortin-4 receptors (MC4Rs). In mice, deletion of the proopiomelanocortin (POMC) or MC4R genes leads to obesity, whereas administration of MC4R agonists (for example, MSH) causes weight loss (1). In humans, inactivating mutations of the POMC (2) or MC4R (3) genes can cause obesity, but there is no evidence that increased melanocortin action can cause weight loss.In the Nelson syndrome, rapid growth of an adrenocorticotrophic pituitary adenoma following bilateral adrenalectomy causes extreme elevation of melanocortin levels ...References1. Seeley RJ, Drazen DL, Clegg DJ. The critical role of the melanocortin system in the control of energy balance. Annu Rev Nutr. 2004;24:133-49. [PMID: 15189116] CrossrefMedlineGoogle Scholar2. Krude H, Biebermann H, Luck W, Horn R, Brabant G, Gruters A. Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet. 1998;19:155-7. [PMID: 9620771] CrossrefMedlineGoogle Scholar3. Vaisse C, Clement K, Durand E, Hercberg S, Guy-Grand B, Froguel P. Melanocortin-4 receptor mutations are a frequent and heterogeneous cause of morbid obesity. J Clin Invest. 2000;106:253-62. [PMID: 10903341] CrossrefMedlineGoogle Scholar4. Mountjoy KG, Mortrud MT, Low MJ, Simerly RB, Cone RD. Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain. Mol Endocrinol. 1994;8:1298-308. [PMID: 7854347] MedlineGoogle Scholar5. Hagan MM, Rushing PA, Schwartz MW, Yagaloff KA, Burn P, Woods SC, et al. Role of the CNS melanocortin system in the response to overfeeding. J Neurosci. 1999;19:2362-7. [PMID: 10066286] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAuthors: Rajagopal V. Sekhar, MD; J. Clay Goodman, MD; Ashok Balasubramanyam, MD; Jeffrey B. Tatro, PhD; Emese Mihaly, PhDAffiliations: From Baylor College of Medicine, Houston, TX 77030; Tufts University School of Medicine, Boston, MA 02111; and Semmelwies University Medical School, 1088 Budapest, Hungary.Editor's Note: The lead author of the following Clinical Observation was one of a dozen Associates of the American College of Physicians selected to present a clinical vignette at the 2003 Annual Session in San Diego. We are proud to present this case report through a special arrangement with the Council of Associates of the College.Acknowledgment: The authors thank Margaret Entwistle for technical expertise.Grant Support: By National Institutes of Health grants DK59537 and HL73696 to Dr. Balasubramanyam and grant MH44694 to Dr. Tatro.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 2 August 2005Volume 143, Issue 3Page: 238-239KeywordsAdrenalectomyAdrenocorticotropic hormoneBlood plasmaBody mass indexBody weightObesityPituitary tumorsScarsWeight gainWeight loss ePublished: 2 August 2005 Issue Published: 2 August 2005 Copyright & PermissionsCopyright © 2005 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...