948 - Estradiol Modulates Estrogen Receptor Beta Expression in Skeletal Muscle of Premenopausal Women

Skeletal muscle is an estradiol (E2) sensitive tissue due to estrogen receptors (ERs) α and β. ER-β activation stimulates skeletal muscle growth and regeneration. Increasing ER-β density (ER-βD) may be a therapeutic target critical for minimizing atrophy following an orthopedic or spinal cord injury. However, a lack of understanding of what biological cues modulate ER-β expression limits this potential. We examined premenopausal women, a physiological relevant system, across the menstrual cycle (MC), hypothesizing that E2 modulates ER-βD and ER-βD is associated with muscle fiber composition (MFC).

Design:

Thirteen female patients (age: 27.2 ± 5.6, BMI: 25.1 ± 5.6) undergoing hip surgery at UTSW/BSW-McKinney (STU#2020-0615) provided blood samples and gluteus medius (GM) muscle biopsies. E2 and progesterone were assayed clinically. MFC and ER-βD in GM were determined via immunofluorescence. Average ER-βD was quantified by two independent evaluators using ImageJ. One-way ANOVA with Tukey’s test compared ER-βD across MC phases and E2 levels (α = 0.05). An unpaired t-test assessed ER-βD and fiber type (α = 0.05).

Results:

Independent of MC, ER-βD differed significantly between low E2 (49.1 ± 4.75) vs. medium (59.7±4.48, p = 0.011) and high concentrations (58.8 ± 2.14, p = 0.035). ER-βD was higher in the late follicular (60.5 ± 5.0, p= 0.014) and luteal phases (58.66 ± 2.92, p = 0.018) vs early follicular (49.1 ± 4.76). Biopsies with >50% Type I fibers had significantly higher ER-βD (61.8 ± 3.5) than those with < 50% (53.7 ± 3.6, p=0.008).  

Conclusions:

Findings suggest ER-βD is responsive within a range of E2, independent of MC. ER-βD increases from early to late follicular and remains elevated into the luteal phase.  ER-βD also is associated with type I fibers content. These relationships could inform strategies to enhance ER- βD for reducing disuse muscle atrophy associated with orthopedic or spinal cord injury.