Background: Oestrogen deficiency reduces skeletal muscle mass and force generation in postmenopausal women. Muscle mass is maintained by satellite cells, which are regulated by oestrogen. Although oestrogen therapy enhances muscle hypertrophy induced by resistance training in postmenopausal women, the molecular mechanism is unclear.Methods: Adult female rats (10 weeks old) were divided into six groups: sham sedentary (Sham‐Sed), sham climbing training (Sham‐CT), ovariectomy sedentary (OVX‐Sed), ovariectomy climbing training (OVX‐CT), ovariectomy plus oestrogen treatment sedentary (OVX+E‐Sed), and ovariectomy plus oestrogen treatment climbing training (OVX+E‐CT). At 8 weeks after ovariectomy, rats in the training group were trained (one session every 3 days for 8 weeks) to climb a ladder while bearing a load. Oestrogen treatment involved subcutaneous insertion of a 17β‐oestradiol pellet. After 8 weeks, the flexor hallucis longus muscle was collected and analysed.Results: Following climbing training, the flexor hallucis longus muscle mass and muscle‐to‐body weight ratios were dramatically increased by training (main effect of training, P < 0.01); the OVX+E‐CT group showed the highest values (main effect of group, P < 0.01). The cross‐sectional area of all muscle fibre types was increased by training (main effect of training, P < 0.01). Particularly, the cross‐sectional area of MHC IIa in the OVX+E‐CT group was significantly larger than that in the Sham‐CT and OVX‐CT groups. Satellite cell numbers were increased in all training groups (main effect of training, P < 0.05), and the myonuclear number was increased by training (main effect of training, P < 0.01), but there was no main group effect. The myonuclear domain size of all muscle fibre types and MHC IIa was increased in all training groups (main effect of training, P < 0.01) and showed a main group effect (P < 0.01). The myonuclear domain sizes of all muscle fibre types and MHC IIa in the OVX+E‐CT group were significantly larger than those in the Sham‐CT and OVX‐CT groups. The total RNA contents revealed main effects of training and the group (P < 0.01); the OVX+E‐CT group showed the highest contents (main effect of group, P < 0.01). The mRNA and protein levels of rpS6 were increased in the OVX+E‐Sed and CT groups (main effects of group, P < 0.05). Particularly, the 28S ribosomal RNA content in OVX+E‐Sed group was significantly higher than that in the OVX‐Sed group.Conclusions: Oestrogen enhanced the resistance training‐induced increase in myonuclear domain size but did not affect satellite cells and ribosome biogenesis.

Myoblast fusion is essential for skeletal muscle development, growth, and regeneration. However, the molecular mechanisms underlying myoblast fusion and differentiation are not fully understood. Previously, we reported that interleukin-4 (IL-4) promotes myoblast fusion; therefore, we hypothesized that IL-4 signaling might regulate the expression of the molecules involved in myoblast fusion. In this study, we showed that in addition to fusion, IL-4 promoted the differentiation of C2C12 myoblast cells by inducing myoblast determination protein 1 (MyoD) and myogenin, both of which regulate the expression of myomerger and myomaker, the membrane proteins essential for myoblast fusion. Unexpectedly, IL-4 treatment increased the expression of myomerger, but not myomaker, in C2C12 cells. Knockdown of IL-4 receptor alpha (IL-4Rα) in C2C12 cells by small interfering RNA impaired myoblast fusion and differentiation. We also demonstrated a reduction in the expression of MyoD, myogenin, and myomerger by knockdown of IL-4Rα in C2C12 cells, while the expression level of myomaker remained unchanged. Finally, cell mixing assays and the restoration of myomerger expression partially rescued the impaired fusion in the IL-4Rα-knockdown C2C12 cells. Collectively, these results suggest that the IL-4/IL-4Rα axis promotes myoblast fusion and differentiation via the induction of myogenic regulatory factors, MyoD and myogenin, and myomerger.

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