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 micrograms/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.(ABSTRACT TRUNCATED AT 250 WORDS)
Donahue
L R
LR
Jackson Laboratory, Bar Harbor, Maine 04609.
Watson
G
G
Beamer
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WG
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000032:analysis; D004357:Drug Synergism; D005260:Female; D013006:Growth Hormone / Q000172:deficiency*; D018971:Insulin-Like Growth Factor Binding Protein 2; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000494:pharmacology*; D007668:Kidney / Q000033:anatomy & histology / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011506:Proteins / Q000378:metabolism*; D013002:Somatomedins / Q000032:analysis; D013154:Spleen / Q000033:anatomy & histology / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology*; D014867:Water / Q000378:metabolism*
D002352:Carrier Proteins; D018971:Insulin-Like Growth Factor Binding Protein 2; D018969:Insulin-Like Growth Factor Binding Proteins; D011506:Proteins; D013002:Somatomedins; D014867:Water; D013739:Testosterone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone