Action and interaction of growth hormone and the beta-agonist, clenbuterol, on growth, body composition and protein turnover in dwarf mice.

The responses of dwarf mice to dietary administration of clenbuterol (3 mg/kg diet), daily injections of growth hormone (15 micrograms/mouse per d) or both treatments combined were investigated and their actions, and any interactions, on whole-body growth, composition and protein metabolism, and muscle, liver and heart growth and protein metabolism, were studied at days 0, 4 and 8 of treatment. Growth hormone, with or without clenbuterol, induced an increase in body-weight growth and tail length growth; clenbuterol alone did not affect body-weight or tail length. Both growth hormone and clenbuterol reduced the percentage of whole-body fat and increased the protein:fat ratio. They also increased protein synthesis rates of whole body and muscle, although the magnitude of the increase was greater in response to growth hormone than to clenbuterol. Clenbuterol specifically induced growth of muscle, with a decrease in liver protein content, whereas growth hormone exhibited more general anabolic effects on tissue protein. Previous reports have suggested that effects of clenbuterol on skeletal muscle are mediated, at least in part, via decreased rates of protein degradation; we could find little evidence of any decrease in whole-body or tissue protein degradation and anabolic effects were largely due to increases in protein synthesis rates. However, small increases in muscle protein degradation rate were observed in response to growth hormone. Growth hormone induced a progressive increase in serum insulin-like growth factor-1 concentration, whereas there was no change with clenbuterol administration. Anabolic effects on whole-body and skeletal muscle protein metabolism, therefore, appear to be initially via independent mechanisms but are finally mediated by a common response (increased protein synthesis) in dwarf mice.