THE ROLE OF THE GROWTH-HORMONE INSULIN-LIKE-GROWTH-FACTOR-I AXIS IN STIMULATION OF PROTEIN-SYNTHESIS IN SKELETAL-MUSCLES FOLLOWING ORAL REFEEDING

The mechanisms behind stimulation of protein synthesis in skeletal mus cles following oral feeding are not well understood. Previous research has not confirmed that insulin is a major factor behind this stimulat ion. In the present study we have used genetically altered mice, with either a lack of GH secretion due to a mutational gene inactivation [G H (-/-) dwarf, DW/JOrlBom-dw] or mice with a homozygous site-specific insertion mutation in the insulin-like growth factor-1 gene [IGF-I(m/m )], leading to a deficient IGF-I production. These gene knock-outs wer e used in comparison to their normal wild types for evaluation of the role that the GH/IGF-I axis may have in activation of nutritionally in duced stimulation of protein synthesis in skeletal muscles during oral refeeding. Weight stable adult C57B16 mice served as an additional no rmal control group. Protein synthesis was measured by a modified flood ing dose technique with radioactive L-[C-14-U]phenylalanine incorporat ion into acid precipitated muscle proteins. Fractional protein synthes is in skeletal muscles after an overnight fast was comparable among C5 7B16 (0.076 +/- 0.009%/h), wild-type IGF-I(+/+) (0.061 +/- 0.008) and IGF-I(m/m) deficient mice (0.068 +/- 0.006%/h), whereas GH(-/-)incompe tent mice had a lower fractional synthesis rate compared with GH(+/+) competent mice (0.045 +/- 0.006 vs. 0.068 +/- 0.007, P < 0.05). Refeed ing with standard chow diet stimulated protein synthesis in muscles by more than 60% in all animal groups. This response was independent of circulating GH, total IGF-I concentrations in blood, as well as up-reg ulation of locally produced IGF-I messenger RNA (mRNA) in skeletal mus cles.