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

Abstract

The ovariectomized (OVX) rat model was used to investigate the effects of estrogen treatment on soleus muscle functionality in situ following muscle injury induced by downhill running. Fifty immature, 24- to 26-d-old, OVX rats were randomly assigned to 5 separate experimental groups: sedentary controls (OVX-Sed), placebo-treated and studied immediately after exercise (OVX-Pb0), placebo-treated and studied 72 h after exercise (OVX-Pb72), estradiol-treated and studied immediately after exercise (OVX-Ed0), and estradiol-treated and studied 72 h after exercise (OVX-Ed72). At the age of 9 weeks, under ketamine and xylazine anesthesia i.p., the rats were subcutaneously implanted with either placebo or 17beta-estradiol-impregnated pellets (0.05 mg/pellet, 3 week release). Treatment with 17beta-estradiol increased the estradiol plasma levels in OVX animals to those normally seen during the proestrous cycle of normal animals. Three weeks after the implantation the rats were subjected to a 90 min intermittent downhill running protocol. Our results indicate that the exercise protocol used in the study induced injury in the soleus muscle, as it was detected by the significant reduction in unfused (stimulation at 10, 20, and 40 Hz) and maximal (Po) tetanic force, as well as the decreased ability of the soleus muscle to maintain tension (stimulation at 40 Hz for 3 min) in OVX-Pb0 and OVX-Pb72 placebo-treated animals subjected to downhill running (injured muscles) as compared with OVX-Sed control rats (uninjured muscle). Estradiol replacement in OVX rats partially protected the soleus muscle from the injury normally induced by downhill running. As compared with the OVX-Pb0 and OVX-Pb72 placebo-treated groups, the soleus muscles of OVX-Ed0 and OVX-Ed72 estradiol-treated rats were capable of producing significantly greater unfused tetanic force and had an increased ability to maintain tension after fatigue. However, estrogen at the dose administered did not prevent the decrease in maximal tetanic force. We postulate that the protective effect of estrogens on muscle strength may be related to the ability of estrogen hormones to attenuate the E--C coupling failure and (or) the disorganization of the contractile apparatus associated with eccentric exercise through a mechanism or mechanisms yet to be fully understood.

A rehabilitation exercise program to remediate skeletal muscle atrophy in an estrogen-deficient organism may be ineffective

“…Indeed, E2 deficient muscles with significantly lower force/ unit area demonstrated rescue of muscle force when E2 was given back to rats that were OVX (Moran et al 2006(Moran et al , 2007. Our findings and those of others support the possibility that E2, rather than T2 or progesterone, aided rehabilitation efforts in this study (Enns and Tiidus 2008;Koot et al 1991;Sotiriadou et al 2006;Enns and Tiidus 2008;Trenkle 1976). McClung et al (2006) reported that loss of ovarian hormones impaired the recovery of fiber CSA in the atrophic SOL following 2 weeks of HLU.…”

“…We did not measure progesterone but findings from other studies strongly suggest that recovery of injured muscle occurs independently of progesterone (Enns and Tiidus 2008;Koot et al 1991;Sotiriadou et al 2006). Only testosterone was measured in this study and if T2 is a reflection of progesterone levels, neither recovery group benefitted from its potential anabolic effect.…”

“…Soleus muscle damage occurs during reloading which may explain the lack of recovery in this muscle compared to the others (Riley 1998). There is strong evidence that skeletal muscles in rats that are estrogen deficient are more susceptible to exercise-related damage (Bar et al 1998;Koot et al 1991;Sotiriadou et al 2006;Thomas et al 2010;Tiidus et al 2005). Several studies from the Tiidus laboratory indicated that downhill running induced significantly more damage to OVX rats than in rats that were estrogen replete.…”

Effect of 5-day vitamin E supplementation on muscle injury after downhill running in rats

“…After exercise, the animals of the Pb-Ex48 and VE-Ex48 groups were placed back in their cages with free access to food and water until they were examined. The exercise protocol implemented in this study has been widely used in previous studies and induced injury in the soleus and other rat hindlimb muscles (Armstrong et al 1983;Ogilvie et al 1988;Sotiriadou et al 2006;Takekura et al 2001). This study focused on the soleus, because it had been reported that downhill running induced more muscle injury to the soleus than other muscles in previous studies (Armstrong et al 1983;Lynch et al 1997;Smith et al 1997).…”

Impaired estrogen receptor action in the pathogenesis of the metabolic syndrome

“…Additionally, E 2 acting via ERα is also shown to promote phosphorylation of p38 MAPK (Ronda et al, 2010a, 2010b), a signaling cascade shown to enhance GLUT4 intrinsic activity and glucose uptake (Furtado et al, 2002; Niu et al, 2003; Sweeney et al, 1999). Furthermore, it is possible that ERα activation of Akt and MAPK pathways may underlie in large part the E 2 -mediated protection of muscle against age-induced sarcopenia (Chen et al, 2005; Leger et al, 2008; Messier et al, 2011; Sipila et al, 2001; Sorensen et al, 2001; Teixeira et al, 2003; Tiidus, 2000), exercise-induced muscle damage (Dieli-Conwright et al, 2009; Sotiriadou et al, 2006; Thomas et al, 2010; Tiidus, 2000), and myocyte apoptosis in the face of a variety of cellular perturbations (Boland et al, 2008; McLoughlin et al, 2009; Vasconsuelo et al, 2008; Wang et al, 2010). Thus, ERα stimulation of muscle growth and insulin sensitivity via direct and indirect interaction with these pathways requires further exploration.…”