Menstrual phase and sex are important determinants of substrate utilization during exercise. We investigated the influence of menstrual phase, sex, 17‐β‐estradiol supplementation (ES) in men and moderate intensity endurance exercise on skeletal muscle mRNA content of seven genes involved in carbohydrate metabolism: glucose transport (GLUT 4), glucose phosphorylation (hexokinase II), glycogen synthesis (glycogenin, glycogen synthase 1, glycogen synthase kinase 3α) and breakdown (glycogen phosphorylase), and glycolysis (PFK). Biopsies from the vastus lateralis were obtained before and after 90 min of cycling at 65% VO2max in a) 12 women in the follicular (FOL) and luteal (LUT) phases and b) 12 men after 8 d of ES and placebo (PL). mRNA content was measured using TaqMan® real time RT‐PCR. During LUT, mRNA was 1.2 fold higher for glycogenin (P = 0.02), but 41% and 54% lower for glycogen phosphorylase (P = 0.041) and GLUT 4 (P = 0.056), respectively, vs. FOL. FOL women had 2.4 fold higher hexokinase mRNA (P = 0.016), 2.4 fold higher GLUT 4 mRNA at rest only (P = 0.032), but 81% lower GSK3αmRNA (P = 0.065), vs. PL men. LUT women had 71% lower PFK mRNA vs. PL men (P = 0.031). ES in men increased glycogen synthase by 1.3 fold (P = 0.02) and GLUT 4 by 1.7 fold (P = 0.023) vs. PL men. Exercise increased hexokinase mRNA by 1.6–2.2 fold (P ≤ 0.03) in PL men and women and GLUT 4 mRNA by 2 fold in PL men and LUT women. We conclude that LUT women have higher capacity for glycogen synthesis and lower capacity for glycogen breakdown vs. FOL. Estrogen mediates glucose transport and glycogen synthesis. Exercise increases the capacity to transport glucose in men and women and to phosphorylate glucose in men and LUT women. (Funded by the Hamilton Health Sciences Foundation and NSERC Canada).
