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Am J Physiol Regul Integr Comp Physiol 286: R417-R430, 2004; doi:10.1152/ajpregu.00365.2003
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INVITED REVIEW

{gamma}-MSH, sodium metabolism, and salt-sensitive hypertension

Michael H. Humphreys

Division of Nephrology, San Francisco General Hospital; and Department of Medicine, University of California San Francisco, San Francisco, California 94143

{alpha}-, {beta}-, and {gamma}-melanocyte stimulating hormones (MSHs) are melanotropin peptides that are derived from the ACTH/{beta}-endorphin prohormone proopiomelanocortin (POMC). They have been highly conserved through evolutionary development, although their functions in mammals have remained obscure. The identification in the last decade of a family of five membrane-spanning melanocortin receptors (MC-Rs), for which the melanotropins are the natural ligands, has permitted the characterization of a number of important actions of these peptides, although the physiological function(s) of {gamma}-MSH have remained elusive. Much evidence indicates that {gamma}-MSH stimulates sympathetic outflow and raises blood pressure through a central mechanism. However, this review focuses on newer cardiovascular and renal actions of the peptide, acting in most cases through the MC3-R. In rodents, a high-sodium diet (HSD) increases the pituitary abundance of POMC mRNA and of {gamma}-MSH content and results in a doubling of plasma {gamma}-MSH concentration. The peptide is natriuretic and acts through renal MC3-Rs, which are also upregulated by the HSD. Thus the system appears designed to participate in the integrated response to dietary sodium excess. Genetic or pharmacologic induction of {gamma}-MSH deficiency results in marked salt-sensitive hypertension that is corrected by the administration of the peptide, probably through a central site of action. Deletion of the MC3-R also produces salt-sensitive hypertension, which, however, is not corrected by infusion of the hormone. These observations in aggregate suggest the operation of a hormonal system important in blood pressure control and in the regulation of sodium excretion. The relationship of these two actions to each other and the significance of this system in humans are important questions for future research.

peptide hormone; pituitary; proopiomelanocortin; melanotropin; central nervous system; neurointermediate lobe



Address for reprint requests and other correspondence: M. H. Humphreys, Box 1341, UCSF, San Francisco, CA 94143-1341 (E-mail: mhhsfgh{at}itsa.ucsf.edu).




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