Acute Changes In Mechanogrowth Factor And Insulin-like Growth Factor I Are Related To Long-term Myofiber Hypertrophy

Abstract

Load-mediated increases in expression of insulin like growth factor-I (IGF-I) and its muscle-specific splice variant, mechano-growth factor (MGF = IGF-IEc), are both thought to play important roles during myofiber hypertrophy. PURPOSE We tested whether load-induced increases in one or both of these mitogenic factors was predictive of long-term hypertrophy by evaluating acute gene expression changes following a single resistance loading (RL) bout and correlating those responses to magnitudes of myofiber hypertrophy after 16 wk RL. METHODS Twenty-two healthy adults consented to 3 vastus lateralis biopsies; before any exercise, 24h after the first bout of RL, and after 16 wk of RL (3 d/wk, 3 sets × 8–12 repetitions to volitional fatigue of squat, leg press, knee extension). Gene expression levels were determined by relative RT-PCR with 18S as an internal standard. Zero-order correlations were tested between levels of acute RL-mediated changes in IGF-I and MGF mRNA expression and 16 wk changes in CSA of type I, IIa, and all type II myofibers, as well as mean fiber area (MFA). RESULTS Acute mRNA changes ranged −16 to +356% for MGF and −35 to +200% for IGF-I with mean ± SE increases of 93 ± 19% and 61 ± 13%, respectively. Acute changes in MGF were predictive of changes in type IIa (r=0.65, p<0.005), all type II (r=0.54, p<0.05), and MFA (r=0.62, p<0.005) but not type I myofibers, while acute changes in IGF-I mRNA were only related to changes in type II fiber CSA (r=0.55, p<0.05). CONCLUSIONS While type I hypertrophy was modest (14 ± 3%) and was not related to acute changes in MGF and IGF-I mRNAs, changes in these mitogenic factors were related to hypertrophy of type II myofibers (25 ± 6%). These data suggest locally-expressed growth factors that are induced by mechanical load are involved in the well-known preferential hypertrophy of type II myofibers consequent to resistance training. Based on these findings, we speculate MGF may play a more important role than IGF-I in this growth adaptation. Supported by NIH Grant R01 AG17896 and GCRC M01 RR00032.