Fujita S, Rasmussen BB, Bell JA, Cadenas JG, Volpi E. Basal muscle intracellular amino acid kinetics in women and men. Am J Physiol Endocrinol Metab 292: E77-E83, 2007. First published August 8, 2006; doi:10.1152/ajpendo.00173.2006.-Sexual dimorphism in skeletal muscle mass is apparent, with men having more muscle mass and larger individual muscle cells. However, no sex-based differences have been detected in blood forearm phenylalanine turnover, although whole body leucine oxidation has been reported to be greater in men than in women. We hypothesized that sex differences in intracellular amino acid turnover may account for these discrepancies, with men having a higher intracellular turnover than women. We studied young, healthy women (women, n ϭ 8) and men (men, n ϭ 10) following an overnight fast. Phenylalanine, leucine, and alanine muscle intracellular kinetics were assessed using stable isotope methodologies, femoral arteriovenous blood sampling, and muscle biopsies. Muscle intracellular amino acid kinetics were reported relative to both leg volume and lean leg mass because of sex differences in leg volume and in muscle and fat distribution. When expressed per leg volume (nmol ⅐ min Ϫ1 ⅐ 100 ml leg volume Ϫ1 ), phenylalanine net balance (women: Ϫ16 Ϯ 4, men: Ϫ31 Ϯ 5), release from proteolysis in the blood (women: 46 Ϯ 9, men: 75 Ϯ 10) and intracellular availability (women: 149 Ϯ 23, men: 241 Ϯ 35), and alanine production, utilization, and intracellular availability were higher in men (P Ͻ 0.05). However, when the kinetic parameters were normalized per unit of lean leg mass, all differences disappeared. Muscle fractional synthetic rate was also not different between women and men. We conclude that there are no sex-based differences in basal muscle intracellular amino acid turnover when the data are normalized by lean mass. It remains to be determined if there are sex differences in intracellular amino acid metabolism following anabolic or catabolic stimuli. protein metabolism; muscle; sex; stable isotopes; gender SEXUAL DIFFERENCES IN HUMAN skeletal muscle mass are apparent. Muscle fiber type distribution is not different between women and men; however, cross-sectional area is larger for all fiber types in men (27,35). Interestingly, the largest muscle fibers in men appear to be fast-twitch type IIa fibers, whereas in women the slow-twitch type I fibers have the largest crosssectional area (27). Furthermore, during short-term limb immobilization, men and women have a similar reduction in muscle cell size, although women have larger reductions in strength (35).The sexual dimorphism in muscle mass is mainly attributed to endocrine differences between women and men because testosterone concentrations are usually ϳ10-fold higher in men (35). It has been shown that castration reduces muscle mass while testosterone administration at replacement or supraphysiological doses increases muscle mass in hypogonadal (3,5) and normal men (2), respectively. These effects are likely due to a stimulation of muscle protein syn...