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The Journal of Neuroscience, November 15, 2000, 20(22):8637-8642

Hypothalamic Melanin-Concentrating Hormone and Estrogen-Induced Weight Loss

Paul Mystkowski¹, Randy J. Seeley⁵, Tina M. Hahn¹, Denis G. Baskin¹, Peter J. Havel³, Alvin M. Matsumoto⁴, Charles W. Wilkinson^{2, 4}, Kimberly Peacock-Kinzig⁵, Kathleen A. Blake⁵, and Michael W. Schwartz¹

Departments of ¹ Medicine and ² Psychiatry and Behavioral Sciences, University of Washington and Veterans Affairs (VA) Puget Sound Health Care System, Seattle, Washington 98104, ³ Department of Nutrition, University of California at Davis, Davis, California 95616, ⁴ Geriatric Research/Education and Clinical Center, VA Puget Sound Health Care System, Seattle, Washington, and ⁵ Department of Psychiatry, University of Cincinnati Medical Center, Cincinnati, Ohio 45267

Melanin-concentrating hormone (MCH) is an orexigenic neuropeptide produced by neurons of the lateral hypothalamic area (LHA). Because genetic MCH deficiency induces hypophagia and loss of body fat, we hypothesized that MCH neurons may represent a specific LHA pathway that, when inhibited, contributes to the pathogenesis of certain anorexia syndromes. To test this hypothesis, we measured behavioral, hormonal, and hypothalamic neuropeptide responses in two models of hyperestrogenemia in male rats, a highly reproducible anorexia paradigm. Whereas estrogen-induced weight loss engaged multiple systems that normally favor recovery of lost weight, the expected increase of MCH mRNA expression induced by energy restriction was selectively and completely abolished. These findings identify MCH neurons as specific targets of estrogen action and suggest that inhibition of these neurons may contribute to the hypophagic effect of estrogen.

Key words: MCH; estrogen; body weight; energy balance; lateral hypothalamus; anorexia; pair-feeding

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Copyright © 2000 Society for Neuroscience  0270-6474/00/20228637-06$05.00/0

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