REGULATION OF METABOLIC WATER AND PROTEIN COMPARTMENTS BY INSULIN-LIKE GROWTH FACTOR-I AND TESTOSTERONE IN GROWTH HORMONE-DEFICIENT LIT/LIT MICE

Insulin-like growth factor-I (IGF-I) and testosterone are major hormonal regulators of protein metabolism. We chose genetically GH-deficient little (lit/lit) mice to test whether these anabolic hormones act independently or in concert with each other to stimulate protein metabolism. Hormones were administered for 14 days at constant rates to 14-week-old lit/lit female mice, IGF-I was infused via mini-osmotic pumps at 30 mu g/day and testosterone was administered using 30 mg pellets. Food consumption was measured during the experimental period, and at the end we measured: (a) serum IGF-I, IGF-I-binding proteins (IGFBPs) and blood urea nitrogen (BUN); (b) body and musculo-skeletal carcass weights; (c) musculo-skeletal carcass water, fat, protein and mineral; and (d) selected organ weights plus protein and DNA contents. We found that both of these growth-stimulatory hormones, IGF-I and testosterone, alone and in combination, had anabolic effects on different metabolic compartments in specific target organs. The most unexpected finding in this study was that the IGF-I-induced increase in musculo-skeletal carcass weight arose solely from increased water, revealing the importance of this compartment as an early target of IGF-I action. Other effects caused specifically by IGF-I, but not testosterone, included increases in serum IGFBP-3, body weight and spleen weight. The specific effect of testosterone, but not IGF-I, was to increase serum IGFBP-2. Independent effects were induced by each hormone alone for kidney and spleen weight, kidney and spleen protein content and BUN. Synergistic effects of IGF-I plus testosterone were observed for the musculo-skeletal preparation, organ weights (liver, kidney, heart and adrenal), liver protein and kidney DNA content. Food consumption did not differ among experimental groups. We conclude that in nutritionally replete GH-deficient lit/lit female mice, IGF-I regulates both water and protein metabolism in an organ-specific manner, whereas the effect of testosterone in specific organs is limited to protein metabolism.