Steroids | 2019
Acute estradiol treatment reduces skeletal muscle protein breakdown markers in early- but not late-postmenopausal women
Abstract
HighlightsThe acute E2 effect on muscle protein breakdown is dependent on time since menopause.The acute E2 action for muscle protein breakdown is not related to estrogen receptor.The E2‐mediated change in FOXO3 is inversely correlated with insulin sensitivity. 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 ER&agr;. 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 ER&agr; 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). ER&agr; 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.