Abstract: BACKGROUND: Estrogen deficiency can lead to a decrease in skeletal muscle mass and muscle strength in postmenopausal women, thereby affecting their quality of life. Muscle mass is maintained by satellite cells, which are regulated by estrogen. Regular exercise, especially high impact exercise (such as resistance training and high-intensity interval training), can induce muscle hypertrophy, but the role and mechanism of estrogen are still unclear. 
OBJECTIVE: To explore the effects of high-intensity interval training combined with estrogen therapy on skeletal muscle hypertrophy in ovariectomized rats and reveal its possible mechanism. 
METHODS: Sixty 8-week-old female Sprague-Dawley rats were divided into five groups using a random number table method: sham operation, model sedentary group, model exercise group, model hormone group, or model combined group. Bilateral ovariectomy was used to establish an estrogen deficiency model. Twelve weeks after operation, the model exercise and model combined group performed high-intensity interval training for 8 weeks (3 times/week), and hormone treatment groups received abdominal subcutaneous injection of 17β-estradiol (once a day for 8 weeks). Seventy-two hours after the last training, the grip force of the forelimb was measured by an electronic grip force meter. The gastrocnemius muscle was separated, and the gastrocnemius mass index was calculated based on the ratio of muscle mass/body mass. The cell cross-sectional area was obtained by hematoxylin-eosin staining. The muscle fiber types were classified by immunofluorescence staining and myonuclear number, myonuclear domain size and number of activated satellite cells were obtained. The total protein concentration in the gastrocnemius muscle was determined by BCA method, and the total RNA in the gastrocnemius muscle was extracted by Trizol method. The expression of ribosomal protein S6 protein was detected by western blot, and the expression of ribosomal RNA (rRNA) was determined by real-time fluorescence quantitative PCR. 
RESULTS AND CONCLUSION: (1) Compared with the sham operation group, the body mass and proportion of myosin heavy chain type I muscle fiber increased (P < 0.05), and the uterine mass index, gastrocnemius mass index, grip force, cell cross-sectional area, myosin heavy chain type IIa proportion, satellite cell and myonuclear number, myonuclear domain size, total protein and RNA contents in the gastrocnemius muscle, and the expression of ribosomal protein S6, 18S rRNA and 28S rRNA decreased (P < 0.05) in the model sedentary group. (2) Compared with the model sedentary group, body mass and myosin heavy chain type IIb proportion decreased (P < 0.05), and the uterine mass index, gastrocnemius mass index, grip force, cell cross-sectional area, myosin heavy chain type IIa proportion, satellite cell number, myonuclear domain size, total protein and RNA contents in the gastrocnemius muscle, and ribosomal protein S6 and 28S rRNA expression levels increased (P < 0.05) in the model exercise group. (3) Compared with the model exercise and model hormone groups, the gastrocnemius mass index, grip force, cell cross-sectional area, satellite cell number, myonuclear domain size, total protein and RNA contents in the gastrocnemius muscle, and ribosomal protein S6 and 28S rRNA expression levels increased (P < 0.05) in the model combined group. In conclusion, estrogen can enhance the skeletal muscle hypertrophy response induced by high-intensity interval training in ovariectomized rats, and the mechanism may be related to activation of satellite cell, increased myonuclear domain and ribosome biogenesis, and improved ribosome function. 

Key words: high-intensity interval training, estrogen, menopause, skeletal muscle, satellite cells, ribosome