Regulation of Protein Metabolism in Middle-Aged, Premenopausal Women: Roles of Adiposity and Estradiol1

The age-related loss of fat-free mass (FFM) is accelerated in women during the middle-age years and continues at an increased rate throughout the postmenopausal period. Because protein is the primary structural component of fat-free tissue, changes in FFM are largely due to alterations in protein metabolism. Knowledge of the hormonal and physiological correlates of protein metabolism in middle-aged women, therefore, has important implications for understanding the mechanisms underlying changes in FFM. We measured leucine kinetics (expressed relative to FFM: micromol/kg FFM/h) in 46 middle-aged, premenopausal women (mean +/- SD, 47 +/- 3 yr) after an overnight fast (i.e. basal) and during euglycemic hyperinsulinemia (40 mU/m2/min) using a 5.5-h infusion of [1-13C]leucine. Additionally, we measured insulin-stimulated glucose disposal by euglycemic hyperinsulinemic clamp, body composition by dual energy x-ray absorptiometry, abdominal fat distribution by computed tomography, and hormone levels by RIA as possible correlates of protein metabolism. Under basal conditions, stepwise regression analysis showed that leucine appearance (i.e. protein breakdown) was related to percent body fat and serum estradiol (r2 = 40%; P < 0.01), and leucine oxidation was related to serum estradiol and percent body fat (r2 = 26%; P < 0.05). Under euglycemic hyperinsulinemic conditions, no variables correlated with the percent change in leucine appearance. The percent change in leucine oxidation was related to intraabdominal adipose tissue area and glucose disposal rate (r2 = 48%; P < 0.01). Correlates and r2 values for nonoxidative leucine disposal (i.e. protein synthesis) under basal and euglycemic hyperinsulinemic conditions were similar to those observed for leucine appearance. From these results, we conclude that adiposity and/or serum estradiol may contribute to the regulation of protein metabolism and FFM in middle-aged, premenopausal women.