17β-estradiol attenuates exercise-induced neutrophil infiltration in men

Abstract

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...

Perspectives on Exertional Rhabdomyolysis

“…Some aerobic exercises can be biased toward lengthening contractions, such as downhill running [43]. In the laboratory, we use such contractions to study mild forms of rhabdomyolysis (not clinically relevant) [13, 44–46]. We have found that performance of laboratory eccentric exercise results in DOMS/pain, prolonged losses in strength and range of motion, and release of muscle proteins into the circulation [47].…”

“…Reportedly, men usually show a greater immune response to eccentric contractions [56]. Although there is currently no explanation for these sex differences, some models indicate a protective role of estrogen [44, 56]. …”

Immunohistochemical Identification of Human Skeletal Muscle Macrophages

“…CD11b is a commonly used marker and is expressed on subsets of lymphocytes and monocytes, these include natural killer (NK) cells, granulocytes and macrophages (Table 1). CD68 is expressed by cells in the monocyte lineage, including macrophages, and is the most commonly used macrophage marker in human skeletal muscle tissue (Table 1) (Stupka et al , 2001; Beaton et al , 2002; Peterson et al , 2003; Crameri et al , 2004; Przybyla et al , 2006; Crameri et al , 2007; Mahoney et al , 2008; Mikkelsen et al , 2009; Varma et al , 2009; Paulsen et al , 2010a; Paulsen et al , 2010b; MacNeil et al , 2011; Tam et al , 2012; Chistiakov et al , 2017; Mackey and Kjaer, 2017; Reidy et al , 2017). CD68 is a member of the lysosomal/endosomal-associated membrane glycoprotein (LAMP) family of proteins, which are mainly associated with the endosomal/lysosomal compartment.…”

Evidence of a Redox‐Dependent Regulation of Immune Responses to Exercise‐Induced Inflammation

“…NAC administration not only accelerates the normalization of GSH and GSH/GSSH after exercise but also mitigates muscle performance drop during recovery, as in this study [3, 41, 57]. NAC may also enhance the GSH-dependent estrogenic activity which contributes to induction of genes encoding enzymatic proteins regulating GSH turnover such as GSH reductase [58]. Redox changes may regulate redox-sensitive intracellular signaling pathways that control cellular phenotype under stress [3, 41].…”