Testosterone and progesterone, but not estradiol, stimulate muscle protein synthesis in postmenopausal women

Abstract

Context: The effect of the female sex steroids, estradiol and progesterone, on muscle protein turnover is unclear. Therefore, it is unknown whether the changes in the hormonal milieu throughout the life span in women contribute to the changes in muscle protein turnover and muscle mass (eg, age associated muscle loss).

Objective: The objective of this study was to provide a comprehensive evaluation of the effect of sex hormones on muscle protein synthesis and gene expression of growth-regulatory factors [ie, myogenic differentiation 1 (MYOD1), myostatin (MSTN), follistatin (FST), and forkhead box O3 (FOXO3)].

Subjects and design: We measured the basal rate of muscle protein synthesis and the expression of muscle growth-regulatory genes in 12 premenopausal women and four groups of postmenopausal women (n=24 total) who were studied before and after treatment with T, estradiol, or progesterone or no intervention (control group). All women were healthy, and pre- and postmenopausal women were carefully matched on body mass, body composition, and insulin sensitivity.

Results: The muscle protein fractional synthesis rate was approximately 20% faster, and MYOD1, FST, and FOXO3 mRNA expressions were approximately 40%-90% greater (all P<.05) in postmenopausal than premenopausal women. In postmenopausal women, both T and progesterone treatment increased the muscle protein fractional synthesis rate by approximately 50% (both P<.01), whereas it was not affected by estradiol treatment and was unchanged in the control group. Progesterone treatment increased MYOD1 mRNA expression (P<.05) but had no effect on MSTN, FST, and FOXO3 mRNA expression. T and estradiol treatment had no effect on skeletal muscle MYOD1, MSTN, FST, and FOXO3 mRNA expression.

Conclusion: Muscle protein turnover is faster in older, postmenopausal women compared with younger, premenopausal women, but these age-related differences do not appear to be explained by the age- and menopause-related changes in the plasma sex hormone milieu.

Trial registration: ClinicalTrials.gov NCT00805207.

Figures

Figure 1.

Skeletal muscle protein FSR during basal, postabsorptive conditions in pre- and postmenopausal women. Data are mean ± SEM. *, Value significantly different from value in premenopausal women (P < .05).

Figure 2.

Skeletal muscle MYOD1, FST, MSTN, and FOXO3 gene expression (relative to GAPDH) during basal, postabsorptive conditions in pre- and postmenopausal women. Data are median (central horizontal line), 25th and 75th percentiles (box), and minimum and maximum values (vertical lines). *, Value significantly different from corresponding value in premenopausal women (P < .05).

Figure 3.

Skeletal muscle protein FSR in postmenopausal women during basal, postabsorptive conditions before and after no intervention (control) or treatment with T, estradiol, or progesterone (top) and the treatment-induced changes in FSR in each group (bottom). Data are mean ± SEM. *, Value significantly different from corresponding value before treatment (P < .05); †, value significantly different from corresponding value in the control group (P < .05).

Figure 4.

Sex hormone treatment-induced changes in muscle MYOD1, FST, MSTN, and FOXO3 gene expression (relative to the average prepost change in the control group) in postmenopausal women. Data are median (central horizontal line), 25th and 75th percentiles (box), and minimum and maximum values (vertical lines). *, Significantly different from corresponding value in the control group (P < .05).