EFFECTS OF GROWTH-HORMONE, THYROXINE, AND AGE ON DIAPHRAGM MUSCLE FROM DWARF MICE

The ability of GH [growth hormone] in vitro to stimulate leucine incorporation into protein and the uptake of 2-aminoisobutyric acid (AIB) and 3-O-methyl-glucose (3-OMG) was studied in diaphragm muscle from dwarf (dw/dw) mice. Ovine GH (25 .mu.g/ml) significantly enhanced the rate of protein synthesis in muscle from untreated dwarfs. In contrast, GH usually failed to stimulate transport, although occasionally a small increase in AIB uptake was seen. Insulin (50 .mu.U/ml) readily stimulated both AIB transport and protein synthesis in muscle from untreated dwarfs. Dwarfs were treated for 4 days with thyroxine (T4) (0.3-5 .mu.g/day) or 3,5,3''-triiodothyronine (T3) (0.1 .mu.g/day). This enhanced the responsiveness of the transport systems to GH and seemed to increase the basal transport rates for AIB and 3-OMG. After the T4-treatment 0.75 .mu.g/ml GH stimulated AIB transport in mice aged 15 wk; 25 .mu.g/ml GH stimulated AIB transport in dwarfs aged 5 wk-1 yr and leucine incorporation into protein in dwarfs aged 5 wk-2 yr. This last result suggests that response to GH does not cease merely due to increasing age. Synergism by T3/T4 was not permanent, and the maximum response to GH occurred 1 wk after the last injection of T4. The possible mechanisms whereby thyroid hormones enhance responsiveness of the transport systems to GH are discussed.