Melanin concentrating hormone: a functional melanocortin antagonist in the hypothalamus. Ludwig, David S., Kathleen G. Mountjoy, Jeffrey B. Tatro, Jennifer A. Gillette, Robert C. Frederich Jeffrey S. Flier, and Eleftheria Maratos-Flier. Division of Endocrinology and Metabolism Division of Endocrinology, Department of Medicine Department of Medicine, Beth Israel-Deaconess Medical Center University of Kentucky, Boston, MA 02215 Chandler Medical Center, Lexington, KY 40536. Division of Endocrinology Division of Endocrinology, Department of Medicine Metabolism and Molecular Medicine, Children's Hospital Department of Medicine and Boston, MA 02115 Tupper Research Institute, Tufts University School of Medicine, New England Medical Center, Boston, MA 02111. Research Center for Developmental Elliott P. Joslin Research Laboratory, Medicine and Biology Joslin Diabetes Center, University of Auckland One Joslin Place, Private Bag 92019 Boston, MA 02215, Auckland, New Zealand
APStracts 4:0285E, 1997.
Melanin concentrating hormone (MCH) and alpha-melanocyte stimulating hormone (_"_MSH) demonstrate opposite actions on skin coloration in teleost fish. Both peptides are present in the mammalian brain, although their specific physiologic roles remain largely unknown. In this study, we examined the interactions between MCH and _"_MSH after intracerebroventricular administration in rats. MCH increased food intake in a dose-dependent manner and lowered plasma glucocorticoid levels through a mechanism involving adrenocorticotropic hormone. In contrast, _"_MSH decreased food intake and increased glucocorticoid levels. MCH, at a two-fold molar excess, antagonized both actions of _"_MSH. _"_MSH, at a three-fold molar excess, blocked the orexigenic properties of MCH. MCH did not block _"_MSH binding or the ability of _"_MSH to induce cAMP in cells expressing either the MC3 or MC4 receptor, the principal brain _"_MSH receptor subtypes. These data suggest that MCH and _"_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.

Received 20 June 1997; accepted in final form 16 December 1997.
APS Manuscript Number E292-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 7 January 1998