Effects of growth hormone, thyroxine, and age on diaphragm muscle from dwarf mice

The ability of GH 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 mug/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 muU/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 mug/day) or 3,5,3'-triiodo thyronine (T3) (0.1 mug/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 mug/ml GH stimulated AIB transport in mice aged 15 weeks; 25 mug/ml GH stimulated AIB transport in dwarfs aged 5 weeks-1 yr. and leucine incorporation into protein in dwarfs aged 5 weeks-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 week after the last injection of T4. The possible mechanisms whereby thyroid hormones enhance responsiveness of the transport systems to GH are discussed.