Estrogen effect on post-exercise skeletal muscle neutrophil infiltration and calpain activity

Abstract

We hypothesized that estrogen administration would attenuate skeletal muscle neutrophil infiltration, indices of muscle membrane disruption, and muscle calpain activity shortly after the termination of exercise. Ovariectomized female rats were implanted with either an estogen pellet (25 mg beta-estradiol) or a placebo pellet. Two weeks postimplant, animals were killed either at rest or 1 h after running exercise (60 min at 21 m x min(-1), 12% grade). The 4 experimental groups (n = 12) used were: unexercised placebo (UP), unexercised estrogen (UE), exercised placebo (EP), and exercised estrogen (EE). Blood samples were analyzed for creatine kinase (CK) activity and estradiol content. Plantaris and gastrocnemius muscles were removed and histochemical determination of neutrophil content or biochemical determination of myeloperoxidase (MPO), glucose-6-phosphate dehydrogenase (G6PD), and calpain-like activity determined. Estrogen supplemented animals had 10-20-fold higher circulating estradiol levels than placebo animals. EP animals had significantly higher (P < 0.05) circulating CK activities than EE or unexercised animals. Muscle neutrophil concentrations were significantly (P < 0.01) elevated in EP and EE groups compared with unexercised controls, with EP muscle neutrophil levels also being over 60% greater (P < 0.05) than in EE animals. EP animals also had higher (P < 0.05) muscle MPO activities than unexercised or EE animals. Muscle G6PD activities were not significantly different between any groups. Muscle caplain-like activities were 80% higher (P < 0.01) in EP animals than EE animals with calpain-like activities in EE animals similar to unexercised groups. These results indicate that estrogen supplementation in ovariectomized rats attenuated 1-h post-exercise serum CK activities, muscle neutrophil infiltration, MPO activities, and calpain-like activities when compared with exercised, unsupplemented animals. This supports the possibility of a relationship between estrogen, calpain dependent production of neutrophil chemo-attractant peptides, and 1-h post-exercise skeletal muscle neutrophil infiltration.

Soleus muscle force following downhill running in ovariectomized rats treated with estrogen

“…Tiidus et al (2001) have proposed a mechanism by which estrogen may be able to inhibit the caplain-induced production of neutrophil chemoattractant peptides by limiting calpain activation and, therefore, attenuate the post-injury neutrophil infiltration. Regardless of the mechanism(s) by which estrogens attenuate exercise-induced muscle injury, there is compelling evidence that such a protective action possibly exists.…”

Influence of Ovarian Hormones on Strength Loss in Healthy and Dystrophic Female Mice

“…Tiidus and co-workers showed inflammation is blunted by estrogen in exercise-injured muscle of rats between 1 h and 7 days post injury, as indicated by reduced infiltration by neutrophils and macrophages [8, 31, 34]. The presence of ovarian hormones has also been shown to expedite the inflammatory response in injured rat muscle [18].…”

Body weight and leukocyte infiltration after an acute exercise-related muscle injury in ovariectomized mice treated with estrogen and progesterone

“…For example, approximately 9–14 days of estrogen treatment attenuates intramuscular leukocyte infiltration in a rat exercise-induced skeletal muscle injury model [5;13;29–31]. In addition, exercise-induced injury studies revealed that the body weight of estrogen-treated rats was lower than that of placebo-treated or untreated rats [4;5;13;29–31].…”

“…In addition, exercise-induced injury studies revealed that the body weight of estrogen-treated rats was lower than that of placebo-treated or untreated rats [4;5;13;29–31]. Therefore, in the rat estrogen treatment-exercise muscle injury model, a short-term (9–14 days) treatment of estrogen simultaneously and consistently affects both body weight and leukocyte infiltration.…”

“…For example, Gorzek et al [7] and Moran et al [18] treated the mice for ~ 4–6 weeks, which is ~ 1–4 weeks longer than Warren et al [32] and Schneider et al [22]. Nevertheless, the duration of estrogen treatment is unlikely to account for the interspecies difference because mice did not have a lower body weight when treated with ~ 2 weeks of estrogen as rats did with a 2-week treatment period [4;5;13;29–31]. Therefore, these data suggest that the body weight response to estrogen treatment may differ between rats and mice.…”