Acute estradiol treatment reduces skeletal muscle protein breakdown markers in early- but not late-postmenopausal women

초록

Objectives: Menopause and decline in estradiol (E-2) may contribute to sarcopenia (i.e., age-related decline in muscle mass and strength) in women. E-2 may directly impact skeletal muscle protein breakdown via estrogen receptor (ER) signaling, primarily ER alpha. It is not yet known whether: 1) E-2 regulates pathways of skeletal muscle protein breakdown; 2) E-2-mediated changes in protein breakdown markers are associated with ERa activation and insulin sensitivity; and 3) the effects of E-2 on protein breakdown markers differ by increasing time since menopause. Study design: We studied 27 women who were <= 6 years past menopause (early postmenopausal, EPM; n = 13) or >= 10 years past menopause (late postmenopausal, LPM; n = 14). Fasted skeletal muscle samples were collected following 1 week of transdermal E-2 or placebo treatment in a randomized cross-over design. Main outcome measures: We analyzed for cytosolic protein content of the: 1) structural proteins myosin heavy chain (MHC) and tropomyosin; and 2) protein regulatory markers: protein kinase B (Akt), muscle-specific ring finger protein1 (MuRF1), atrogin1, and forkhead box O3 (FOXO3) using Western blot. Results: In response to acute E-2, FOXO3 activation (dephosphorylation) and MuRF1 protein expression decreased in EPM but increased in LPM women (p < 0.05). ERa activation was not associated with these protein breakdown markers, but FOXO3 activation tended to be inversely correlated (r = -0.318, p = 0.065) to insulin sensitivity. Conclusions: These preliminary studies suggest the effects of E-2 on skeletal muscle protein breakdown markers were dependent on time since menopause, which is consistent with our previous study on insulin sensitivity.

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