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Am J Physiol Endocrinol Metab 274: E627-E633, 1998;
0193-1849/98 $5.00
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Vol. 274, Issue 4, E627-E633, April 1998

Melanin-concentrating hormone: a functional melanocortin antagonist in the hypothalamus

David S. Ludwig1,2, Kathleen G. Mountjoy5, Jeffrey B. Tatro4, Jennifer A. Gillette3, Robert C. Frederich1, Jeffrey S. Flier1, and Eleftheria Maratos-Flier3

1 Division of Endocrinology and Metabolism, Department of Medicine, Beth Israel-Deaconess Medical Center, 2 Division of Endocrinology, Department of Medicine, Children's Hospital, and 3 Elliott P. Joslin Research Laboratory, Joslin Diabetes Center, Boston 02115; 4 Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine, Tupper Research Institute, Tufts University School of Medicine, New England Medical Center, Boston, Massachussetts 02111; and 5 Research Center for Developmental Medicine and Biology, University of Auckland, Auckland, New Zealand

Melanin-concentrating hormone (MCH) and alpha -melanocyte-stimulating hormone (alpha -MSH) demonstrate opposite actions on skin coloration in teleost fish. Both peptides are present in the mammalian brain, although their specific physiological roles remain largely unknown. In this study, we examined the interactions between MCH and alpha -MSH after intracerebroventricular administration in rats. MCH increased food intake in a dose-dependent manner and lowered plasma glucocorticoid levels through a mechanism involving ACTH. In contrast, alpha -MSH decreased food intake and increased glucocorticoid levels. MCH, at a twofold molar excess, antagonized both actions of alpha -MSH. alpha -MSH, at a threefold molar excess, blocked the orexigenic properties of MCH. MCH did not block alpha -MSH binding or the ability of alpha -MSH to induce cAMP in cells expressing either the MC3 or MC4 receptor, the principal brain alpha -MSH receptor subtypes. These data suggest that MCH and alpha -MSH exert opposing and antagonistic influences on feeding behavior and the stress response and may function in a coordinate manner to regulate metabolism through a novel mechanism mediated in part by an MCH receptor.

obesity; eating


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