MacNeilLG, Baker SK, Stevic I, Tarnopolsky MA. 17-estradiol attenuates exercise-induced neutrophil infiltration in men. Am J Physiol Regul Integr Comp Physiol 300: R1443-R1451, 2011. First published March 2, 2011; doi:10.1152/ajpregu.00689.2009 attenuates exercise-induced muscle damage and inflammation in some models. Eighteen men completed 150 eccentric contractions after random assignment to placebo (Control group) or E2 supplementation (Experimental group). Muscle biopsies and blood samples were collected at baseline, following 8-day supplementation and 3 h and 48 h after exercise. Blood samples were analyzed for sex hormone concentration, creatine kinase (CK) activity and total antioxidant capacity. The mRNA content of genes involved in lipid and cholesterol homeostasis [forkhead box O1 (FOXO1), caveolin 1, and sterol regulatory element binding protein-2 (SREBP2)] and antioxidant defense (SOD1 and -2) were measured by RT-PCR. Immunohistochemistry was used to quantify muscle neutrophil (myeloperoxidase) and macrophage (CD68) content. Serum E2 concentration increased 2.5-fold with supplementation (P Ͻ 0.001), attenuating neutrophil infiltration at 3 h (P Ͻ 0.05) and 48 h (P Ͻ 0.001), and the induction of SOD1 at 48 h (P ϭ 0.02). Macrophage density at 48 h (P Ͻ 0.05) and SOD2 mRNA at 3 h (P ϭ 0.01) increased but were not affected by E2. Serum CK activity was higher at 48 h for both groups (P Ͻ 0.05). FOXO1, caveolin 1 and SREBP2 expression were 2.8-fold (P Ͻ 0.05), 1.4-fold (P Ͻ 0.05), and 1.5-fold (P Ͻ 0.001) and higher at 3 h after exercise with no effect of E2. This suggests that E2 attenuates neutrophil infiltration; however, the mechanism does not appear to be lesser oxidative stress or membrane damage and may indicate lesser neutrophil/endothelial interaction. mRNA expression; sex differences; leukocytes; oxidative stress SKELETAL MUSCLE IS A HETEROGENEOUS and adaptable tissue, able to function across a spectrum of physiological and metabolic conditions and remodel in response to changing demands. When subjected to unaccustomed exercise, particularly contractions that forcibly lengthen muscle (also known as eccentric contractions), myofibers are stressed beyond their functional capacity and damage may occur (16,51). This damage can be measured in 48 h following exercise as structural disturbances at cellular and subcellular levels (19, 52), muscle protein appearance in blood (46, 52), tissue inflammatory cell infiltration (31, 52), and increased soreness and impaired muscle function (17, 21). Many genes involved in postexercise membrane homeostasis, stress management, and growth are also affected, changing the myofiber transcriptome (46, 53). Because of the substantial effect on muscle tissue, eccentric contractions are commonly used for exercise-induced muscle damage and/or inflammation research.Most animal studies report differences in measures of exercise-induced muscle damage, inflammation, and repair between males and females (3, 39, 61). Manipulation of the female sex hormone 17-estradiol (E2) ind...