Abstract Resistance exercise training (RET) leads to marked interindividual heterogeneity in the hypertrophic response. Whether such heterogeneity is due to endogenous (i.e. inherent biological factors) or exogenous variables (i.e. external load) has not been firmly established. Twenty healthy young male participants completed thrice‐weekly resistance exercise sessions for 10 weeks. Each participant had their legs and arms randomly assigned to perform unilateral bicep curls or knee extensions with either a higher (heavier) load (HL: 8–12 repetitions; ∼70%–80% of one‐repetition maximum (1RM)) or, in the contralateral limb, lower load (LL: 20–25 repetitions at ∼30%–40% 1RM) for three sets to volitional fatigue during each session. Fat‐ and bone‐free mass (dual‐energy X‐ray absorptiometry), muscle size (ultrasonography and muscle biopsies) and strength were measured pretraining and at 10 weeks. Skeletal muscle biopsies were obtained from the vastus lateralis, and we used ingested deuterated water to assess myofibrillar protein synthesis (MyoPS) at weeks 1 and 10 during training. Despite considerable interindividual variability in hypertrophic responses, we observed that muscle hypertrophy following RET was relatively well conserved within versus between subjects and was unaffected by load. Rates of MyoPS in weeks 1 and 10 of training were increased relative to rest (Week 1: Δ0.27 ± 0.11, P < 0.0001; Week 10: Δ0.10 ± 0.14%/d, P = 0.009); however, MyoPS was attenuated in week 10 versus week 1 (Δ0.16 ± 0.18%/d, P < 0.001). MyoPS rates were less heterogenous within versus between individuals. Variation in RET‐induced muscle hypertrophy occurred independent of external load and was relatively well conserved (i.e., retention of the hypertrophic response) across different anatomical limbs within an individual.

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Key points

Considerable interindividual variability exists in resistance exercise training (RET)‐induced muscle hypertrophy. However we observed that RET‐induced muscle hypertrophy is relatively conserved within an individual (i.e. between the upper‐ and lower body) and is independent of external load when RET is performed to volitional fatigue.

Changes in myofibrillar protein synthesis (MyoPS) rates are comparable with both higher and lower loads but are blunted following a period of RET despite progressive overload.

There is negligible shared variance between RET‐induced increases in muscle size and strength. Additionally, there are limited relationships between measures used to assess RET‐induced muscle hypertrophy.

We conclude that when effort is matched (i.e. working to volitional muscular fatigue), RET‐induced hypertrophy is mediated to a far greater degree by inherent endogenous biological factors, which account for a large proportion of the heterogeneity between individuals.