Peripherally administered desacetyl-α-MSH and α-MSH both influence post-natal rat growth and associated rat hypothalamic protein expression

Wu, Chia-Shan Jenny, David R. Greenwood, Janine M. Cooney, Dwayne J. Jensen, Michele A. Tatnell, Garth J. S. Cooper, and Kathleen G. Mountjoy. Peripherally administered desacetyl -MSH and -MSH both influence postnatal rat growth and associated rat hypothalamic protein expression. Am J Physiol Endocrinol Metab 291: E1372–E1380, 2006. First published July 25, 2006; doi:10.1152/ajpendo.00480.2005.—Desacetyl -MSH predominates over -MSH during development, but whether it is biologically active and has a physiological role is unclear. We compared the effects of 0.3 g g 1 day 1 desacetyl -MSH with that of 0.3 g g 1 day 1 -MSH on postnatal body growth by administering the peptides subcutaneously daily for postnatal days 0–14 and also used a twodimensional gel electrophoresis gel-based proteomic approach to analyze protein changes in hypothalami, the relay center for body weight and growth regulation, after 14 days of treatment. We found that the growth rate between days 1 and 10 was significantly decreased by desacetyl -MSH but not by -MSH, but by day 14, a time reported for development of a mature pattern of hypothalamic innervation, both peptides had significantly increased neonatal growth compared with PBS-treated control rats. Desacetyl -MSH significantly increased spleen weight, but -MSH had no effect. -MSH significantly decreased kidney weight, but desacetyl -MSH had no effect. Both desacetyl -MSH and -MSH significantly decreased brain weight. By 14 days, both peptides significantly changed expression of a number of hypothalamic proteins, specifically metabolic enzymes, cytoskeleton, signaling, and stress response proteins. We show that peripherally administered desacetyl -MSH is biologically active and induces responses that can differ from those for -MSH. In conclusion, desacetyl -MSH appears to be an important regulator of neonatal rat growth.