Studies on the Physiological Functions of the Melanocortin System
Roger D. Cone
Center for the Study of Weight Regulation and Associated Disorders, and Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239-3098
Correspondence: Address all correspondence and requests for reprints to: Roger D. Cone, Ph.D., Director, Center for the Study of Weight Regulation and Associated Disorders, Senior Scientist, Vollum Institute, Oregon Health and Science University, L481, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239-3098. E-mail: cone{at}ohsu.edu
The melanocortin system refers to a set of hormonal, neuropeptidergic,and paracrine signaling pathways that are defined by componentsthat include the five G protein-coupled melanocortin receptors;peptide agonists derived from the proopiomelanocortin preprohormoneprecursor; and the endogenous antagonists, agouti and agouti-relatedprotein. This signaling system regulates a remarkably diversearray of physiological functions including pigmentation, adrenocorticalsteroidogenesis, energy homeostasis, natriuresis, erectile responses,energy homeostasis, and exocrine gland secretion. There aremany complex and unique aspects of melanocortin signaling, suchas the existence of endogenous antagonists, the agouti proteins,that act at three of the five melanocortin receptors. However,there is an aspect of melanocortin signaling that has facilitatedhighly reductionist approaches aimed at understanding the physiologicalfunctions of each receptor and peptide: in contrast to manypeptides, the melanocortin agonists and antagonists are expressedin a limited number of very discrete locations. Similarly, themelanocortin receptors are also expressed in a limited numberof discrete locations where they tend to be involved in rathercircumscribed physiological functions. This review examinesmy laboratory’s participation in the cloning of the melanocortinreceptors and characterization of their physiological roles.
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