Influence of hormone replacement therapy with maximal eccentric exercise on estrogen receptor coregulators and skeletal muscle damage in postmenopausal women

UnrestrictedThe use of hormone replacement therapy (HRT) is a potential treatment to relieve symptoms of menopause and prevent the onset of disease such as osteoporosis in postmenopausal women. Although estrogen has a possible protective effect against exercise-induced skeletal muscle damage, it is unclear if HRT enhances estrogen receptor (ER) transcriptional activity in skeletal muscle at rest and following resistance exercise. We sought to evaluate changes in the gene expression of ER coregulators (SRC-1 and SMRT) and markers of skeletal muscle damage (CK, LDH, and TNF-α) in postmenopausal women following a high-intensity resistance exercise bout. Fourteen postmenopausal women were divided into two groups: Control, women not using HRT (n=6, 59±4 yr, 63±17 kg), or HRT, women using traditional HRT (n=8, 59±4 yr, 89±24 kg). Both groups performed 10 sets of 10 maximal eccentric repetitions of single-leg extension on the Cybex dynamometer at 60°/s with 20 second rest periods between sets. Muscle biopsies of the vastus lateralis were obtained from the exercised leg at baseline and 4 hours after the exercise bout. Gene expression was determined using RT-PCR for SRC-1, SMRT, and TNF-α. Blood draws were performed at baseline and 3 days post-exercise to measure CK and LDH. Independent t-tests were performed to test group differences (Control vs HRT). A probability level of p≤0.05 was used to determine statistical significance. We observed significantly greater changes in gene expression of SRC-1 and SMRT (p≤0.01) and significantly lower changes in gene expression of TNF-α (p≤0.01) in the HRT group compared to controls following the exercise bout. Gene expression of SRC-1 significantly increased (p≤0.01; 2.4 to 5.2 fold change) and gene expression of SMRT significantly decreased (p≤0.01; -1.3 to -4.3 fold change) following the exercise bout in both groups. CK and LDH levels were significantly greater post-exercise (p≤0.01) in the Control group.; These data suggest a single bout of maximal eccentric exercise significantly enhances ER transcriptional activity with greater response present in postmenopausal women using HRT. Postmenopausal women not using HRT experienced greater muscle damage after exercise indicating a possible protective effect of HRT against exercise-induced skeletal muscle damage