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Sex-specific differences in rat soleus muscle signaling pathway responses to a bout of horizontal and downhill running

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Abstract

Males and females of many species, including humans, exhibit different muscle responses and adaptations to exercise stress; however, the molecular mechanisms that underlie these changes are poorly understood. Therefore, the present study assessed sex-related differences in intracellular signaling pathway responses to bouts of horizontal or downhill running in rat soleus muscles. Age-matched male and female Wistar rats (10 weeks old, n = 18/group) were either rested (control group) or subjected to an either a bout of horizontal (22 m/min, 20 min, 0° incline) or downhill (16 m/min, 10 min, − 16% incline) treadmill running. Soleus muscle samples were collected both prior to and immediately after exercise (n = 6/group). Intramuscular signaling responses to each type of exercise were determined via real-time (RT) PCR and western blot analyses. Although mTOR signaling (mTOR/S6K1/S6) responses to both horizontal and downhill exercise were found to be similar in both sexes, ERK phosphorylation levels were found to be significantly higher in male than in female rats after downhill exercise. Similarly, heat shock protein (Hsp) 72 and myostatin protein expression levels were both found to be significantly altered after downhill exercise: Hsp levels increased in male and decreased in female rats, whereas myostatin increased in female but decreased in male rats. Thus, the results of the present study suggest that downhill exercise may elicit sex-specific differential changes to Hsp72 expression, ERK phosphorylation, and myostatin-signaling activation in female compared with those in male rat soleus muscles. Further study is required to confirm these findings and to determine the way in which they impact sex-specific differences in exercise-induced muscle adaptations.

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Acknowledgments

This work was supported by Japanese Center for Research on Women in Sports (T. Yoshihara). This work was also supported by grants from the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant No. 17K01765 (T. Yoshihara), and the Ministry of Education, Culture, Sports, Science and Technology (MEXT)-Supported Program for the Strategic Research Foundation at Private Universities.

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Contributions

T.Y., R.K., and H.N. conceived and designed the research; T.Y., S.C., T.T., and T.N. performed the experiments; T.Y. S.C., and T.N. analyzed the data; T.Y. and R.K. interpreted the results of the experiments; T.Y. prepared the figures; T.Y. drafted the manuscript; T.Y., S.C., T.T., T.N., R.K., T.S., and H.N. edited and revised the manuscript; T.Y., S.C., T.T., T.N., R.K., T.S., and H.N. approved the final version of the manuscript.

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Correspondence to Toshinori Yoshihara.

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This study was approved by the Juntendo University Animal Care Committee (H28-15) and was conducted according to the guiding principles for the care and use of laboratory animals set forth by the Physiological Society of Japan.

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The authors declare that they have no conflict of interest.

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Yoshihara, T., Chang, Sw., Tsuzuki, T. et al. Sex-specific differences in rat soleus muscle signaling pathway responses to a bout of horizontal and downhill running. J Physiol Biochem 75, 585–595 (2019). https://doi.org/10.1007/s13105-019-00712-5

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