This week’s EXSS Impact post highlights the work of Elizabeth “Liz” Walz, who is one of our former graduate students in the Exercise Physiology specialization area. Liz now serves as the Fitness Coordinator in UNC’s Campus Recreation program. Many thanks to Liz and her graduate thesis committee (Anthony Hackney (advisor), Dr. Abbie Smith-Ryan, Alain Aguilar) for providing this week’s EXSS Impact post.
1) Why did you do the study?
There has been debate surrounding the influence of 17b-estradiol (E2) on skeletal muscle, and whether E2 has a protective influence on skeletal muscle damage, inflammation, and repair after prolonged aerobic exercise. This area of research is limited. There are multiple studies indicating that high levels of E2 attenuate circulating cytokines, and as a result attenuate inflammation during non-exercise induced inflammatory responses (Pfeilschifter et al., 2002; Pottratz et al., 1994; Puder et al., 2001; Schwarz et al., 2000). This indicates that there may be a similar phenomenon occurring during exercise induced inflammatory responses. A clear relationship between E2 and inflammation after exercise induced muscle damage, in women, is not well defined in existing literature. Evaluating the influence of E2 fluctuations across the menstrual cycle, and how this impacts skeletal muscle, will add to this body of knowledge, and is an important consideration for women designing training programs to improve performance and minimize risk.
2) What did you do and what did you find?
The study purpose was to determine if estrogen (E2) concentrations attenuate inflammation after exercise-induced muscle damage. Blood responses of pro-inflammatory cytokine biomarker TNF-a, and pro- and anti-inflammatory cytokine biomarker IL-6 were measured. Ten, eumenorrheic, endurance-trained women (Mean±SD; 21±1 years, 24.1±2.8 body fat%) were studied. They completed a 60 minute running protocol at ~60-65% of their oxygen uptake (VO2peak 53.5±4.7ml/kg/min) during two hormonal conditions (low E2 and high E2). Inflammation was assessed at rest, immediately post exercise, 30 minutes post exercise, and 24 hours post exercise. There was not a significant interaction effect for TNF-a (p=0.60). There was a significant interaction effect for IL-6 (p=0.001). The response at 30 minutes post exercise was significantly elevated from rest and significantly reduced in high E2. Results suggest high E2 conditions attenuate the IL-6 response. Due to the pro- and anti-inflammatory influence of IL-6, it is unclear whether this attenuation is positive or negative.
3) What’s the impact of these findings on the public?
In conclusion, there was not a significant interaction effect between E2 and the primary variable of interest, cytokine TNF-a, indicating that HE does not attenuate pro-inflammatory TNF-a responses. However, there was a significant interaction effect between E2 and IL-6, the significance of this finding is unclear due to the pro- and anti-inflammatory effects of IL-6.
The mechanism by which E2 exerts a protective effect on skeletal muscle and inflammation is not well understood, but thought to be a result of E2 acting as an antioxidant, membrane stabilizer and gene regulator (Perksy et al., 1999). While it can be interpreted that there is less IL-6 exerting anti-inflammatory and glucose sparing effects during HE, a bulk of the research literature suggests that the attenuation of IL-6 is positive because it means there is less overall inflammation following damaging exercise (Angstwurm et al., 1997; Chiu et al., 2000; Schwarz et al., 2000). Additionally previous research in this laboratory, found HE concentrations to promote glucose-sparing mechanisms and increase fat utilization by increasing the activity of lipoprotein lipase, circulating growth hormone, and decreasing circulating insulin levels (Hackney et al., 1999). This supports the theory that HE levels promote fat utilization and the attenuation of IL-6 may result from less muscle damage and inflammation following the exercise bout and less of a need for IL-6 as enhancer of lipolysis since HE may be exerting some of these actions directly.
Other known pro-inflammatory markers should also be looked at to determine if there is in fact a protective influence of E2 on muscle damage, inflammation, and repair. Information regarding the estrogenic effect on inflammation across the menstrual cycle would be useful for eumenorrheic women not on birth control, when designing exercise programs, as well as considerations in study design when investigating the inflammatory response in women.