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Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2004-1145
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The Journal of Clinical Endocrinology & Metabolism Vol. 90, No. 4 2412-2419
Copyright © 2005 by The Endocrine Society

Increased Melanin Concentrating Hormone Receptor Type I in the Human Hypothalamic Infundibular Nucleus in Cachexia

Unga A. Unmehopa, Joop J. van Heerikhuize, Wenda Spijkstra, John W. Woods, Andrew D. Howard, Emanuel Zycband, Scott D. Feighner, Donna L. Hreniuk, Oksana C. Palyha, Xiao-Ming Guan, Douglas J. MacNeil, Lex H. T. Van der Ploeg and Dick F. Swaab

Netherlands Institute for Brain Research (U.A.U., J.J.v.H., W.S., D.F.S.), 1105 AZ Amsterdam, The Netherlands; and Departments of Immunology and Rheumatology (J.W.W., E.Z.) and Metabolic Disorders (A.D.H., S.D.F., D.L.H., O.C.P., X.-M.G., D.J.M., L.H.T.V.d.P.), Merck Research Laboratories, Rahway, New Jersey 07065

Address all correspondence and requests for reprints to: D. F. Swaab, Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ Amsterdam, The Netherlands. E-mail: dfswaab{at}nih.knaw.nl.

Melanin-concentrating hormone (MCH) exerts a positive regulation on appetite and binds to the G protein-coupled receptors, MCH1R and MCH2R. In rodents, MCH is produced by neurons in the lateral hypothalamus with projections to various hypothalamic and other brain sites. In the present study, MCH1R was shown, by immunocytochemistry, to be present in the human infundibular nucleus/median eminence, paraventricular nucleus, lateral hypothalamic area, and perifornical area, although in the latter two regions, only a few MCH1R-containing cells were found. In addition, MCH1R staining was found in nerve fibers in the periventricular nucleus, dorsomedial and ventromedial nucleus, suprachiasmatic nucleus, and tuberomammillary nucleus. A significant 1.6 times increase in the number of MCH1R cell body staining was found in the infundibular nucleus in postmortem brain material of cachectic patients, compared with matched controls, supporting a role for this receptor in energy homeostasis in the human.






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