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Article

Growth Hormone Improves Body Mass Recovery with Refeeding after Chronic Undernutrition-Induced Muscle Atrophy in Aging Male Rats¹

Bill T. Ameredes^*2, Jon F. Watchko^**, Monica J. Daood^**, J. Fernando Rosas, Michael P. Donahoe and Robert M. Rogers

^* Department of Cell Biology and Physiology, ^** Magee Women’s Research Institute, Children’s Hospital of Pittsburgh, and Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA 15261

²To whom correspondence should be addressed.

The effects of growth hormone (GH) administration and refeeding after chronic undernutrition (UN) were investigated in Fischer 344 male rats aging into senescence (24.5 mo of age) during UN initiated at 12.5 mo of age that produced muscle atrophy and a 50% decrease in body mass. Muscle mass, protein, myosin heavy-chain (MHC) composition and circulating testosterone levels were measured and compared to controls with free access to food. Within 9 wk, refeeding + GH restored body mass to control levels, whereas it was still decreased with refeeding alone. By 24.5 mo of age, refeeding alone restored body mass, while addition of GH resulted in overshoot. UN uniformly decreased mass of the gastrocnemius, extensor digitorum longus, soleus and diaphragm muscles to 50–60% of controls. Refeeding and refeeding + GH restored these losses with some overshoot of gastrocnemius muscle suggesting hypertrophy. UN more than doubled slow Type I MHC composition and approximately halved fast Type IIB and IIX MHC in the deep gastrocnemius muscle while it increased Type IIA MHC in the diaphragm. Refeeding and refeeding + GH reversed these shifts. MHC shifts in the extensor digitorum longus and soleus muscles were not statistically significant, whereas UN increased fast Type IIA MHC followed by decrease with refeeding + GH. UN decreased testosterone levels to nearly zero followed by restoration with refeeding and refeeding + GH. We conclude that the phenotype of mixed-MHC muscles such as the gastrocnemius and diaphragm are most affected by chronic UN, which is reversible with refeeding and refeeding + GH. These alterations were associated with changes in circulating testosterone, which may be a key regulatory element in these processes.

KEY WORDS: • cachexia • Fischer 344 rats • senescence • undernutrition

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