Steroids · Mar 27, 2019

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

By Park YM, Keller AC, Runchey SS et al.

OBJECTIVES: Menopause and decline in estradiol (E₂) may contribute to sarcopenia (i.e., age-related decline in muscle mass and strength) in women. E₂ may directly impact skeletal muscle protein breakdown via estrogen receptor (ER) signaling, primarily ERα. It is not yet known whether: 1) E₂ regulates pathways of skeletal muscle protein breakdown; 2) E₂-mediated changes in protein breakdown markers are associated with ERα activation and insulin sensitivity; and 3) the effects of E₂ 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 E₂ 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 E₂, FOXO3 activation (dephosphorylation) and MuRF1 protein expression decreased in EPM but increased in LPM women (p < 0.05). ERα 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 E₂ on skeletal muscle protein breakdown markers were dependent on time since menopause, which is consistent with our previous study on insulin sensitivity.

doi.org/10.1016/j.steroids.2019.03.008 Open access, accepted manuscript PubMed 30928279 Interventions