The purpose of the present study was to characterize the progression of red blood cell volume (RBCV) expansion and potential volumetric and endocrine regulators of erythropoiesis during endurance training (ET). Nine healthy, untrained volunteers (age = 27 ± 4 yr) underwent supervised ET consisting of 3-4 × 60 min cycle ergometry sessions per week for 8 wk. Plasma volume (PV), RBCV, and overnight fasting hematological markers were determined before and at ,, and of ET. In addition, plasma erythropoietin (EPO), cortisol, copeptin, and proatrial natriuretic peptide concentrations were measured during a 3-h morning period at baseline and postexercise at and PV increased from baseline (2,405 ± 335 ml) at, , and (+374 ± 194, +505 ± 156, and +341 ± 160 ml, respectively, < 0.001). Increases in RBCV from baseline (1,737 ± 442 ml) were manifested at (+109 ± 114 ml, = 0.030) and (+205 ± 109 ml, = 0.001). Overnight fasting plasma EPO concentration increased from baseline (11.3 ± 4.8 mIU/ml) at (+2.5 ± 2.8 mIU·ml, = 0.027) and returned to baseline concentration at and Higher 3-h-postexercise EPO concentration was observed at (11.6 mIU/ml) compared with (8.4 ± 3.9 mIU/ml, = 0.009) and baseline (9.0 ± 4.2 mIU/ml, = 0.019). Linear relationships between EPO concentration and hematocrit (β = -56.2, < 0.001) and cortisol (β = 0.037, < 0.001) were detected throughout the ET intervention. In conclusion, ET leads to mild, transient increases in circulating EPO concentration, concurring with early PV expansion and lowered hematocrit, preceding gradual RBCV enhancement.

Fat oxidation during exercise is greater in females than in males. We sought to determine whether sex differences in substrate metabolism are paralleled by distinct skeletal muscle mitochondrial volume density and oxidative capacity. Whole-body substrate (fat and carbohydrate) utilization during submaximal treadmill running was assessed, and skeletal muscle biopsies were taken to determine mitochondrial volume density and function in healthy young females (n = 12) and males (n = 12) matched by aerobic exercise capacity and exercise performance. Females presented a lower respiratory exchange ratio (0.87 ± 0.04 versus 0.91 ± 0.04, P = 0.023) and whole-body carbohydrate oxidation (27.8 ± 8.3 versus 35.8 ± 6.5 mg kg min , P = 0.027), whereas fat oxidation was higher (8.7 ± 2.8 versus 5.9 ± 2.6 mg kg min , P = 0.034) during submaximal exercise compared with males. In skeletal muscle biopsies, females demonstrated augmented mitochondrial volume density (7.51 ± 1.77 versus 5.90 ± 1.72%, P = 0.035) and oxidative capacity for fatty acid [36.6 ± 12.8 versus 24.5 ± 7.3 pmol O s (mg wet weight) , P = 0.009] and lactate [71.1 ± 24.4 versus 53.2 ± 14.6 pmol O s (mg wet weight) , P = 0.040]. No sex differences in respiratory exchange ratio, whole-body fat oxidation and skeletal muscle variables were detected when adjusted for anthropometric variables including body mass or leg mass, which were lower in females. In conclusion, female prioritization of fat over carbohydrate oxidation during exercise is underpinned by augmented body size-related mitochondrial volume density, fatty acid and lactate oxidative capacity in skeletal muscle fibres.