The Journal of Physiological Sciences

, Volume 69, Issue 2, pp 235–244 | Cite as

Sex differences in forkhead box O3a signaling response to hindlimb unloading in rat soleus muscle

  • Toshinori YoshiharaEmail author
  • Toshiharu Natsume
  • Takamasa Tsuzuki
  • Shuo-wen Chang
  • Ryo Kakigi
  • Takao Sugiura
  • Hisashi Naito
Original Paper


We tested the hypothesis that there are sex differences in hindlimb unloading-induced activation of the forkhead box subfamily O3a (FoxO3a) signaling pathway in rat soleus muscle. Age-matched male and female Wistar rats were subjected to hindlimb unloading, and the soleus muscle was removed before or 1 or 7 days after unloading. Female rats showed greater percent changes in relative soleus muscle weight than males. FoxO3a phosphorylation was lower in females than in males and was associated with higher levels of protein ubiquitination 7 days after unloading. Heat shock protein 72 (Hsp72) levels were lower in female rats and increased in males during unloading. Female rats showed slightly higher myostatin levels, which showed a non-significant decline in male rats following unloading. Thus, males and females show different responses to the FoxO3a/ubiquitin–proteasome pathway following hindlimb unloading in rat soleus muscle, which may be associated with differences in Hsp72 expression and myostatin signaling.


Sex difference Soleus muscle Forkhead box O Heat shock protein 72 Myostatin Hindlimb unloading 



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

Author contributions

TY, RK, and HN conceived and designed the research; TY, TN, TT, and SC performed the experiments; TY and TN analyzed the data; TY and RK interpreted results of the experiments; TY prepared the figures; TY drafted the manuscript; TY, TN, TT, SC, RK, TS, and HN edited and revised the manuscript; TY, TN, TT, SC, RK, TS, and HN approved the final version of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest to declare.


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Copyright information

© The Physiological Society of Japan and Springer Japan KK, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Graduate School of Health and Sports ScienceJuntendo UniversityInzaiJapan
  2. 2.Faculty of PharmacyMeijo UniversityNagoyaJapan
  3. 3.Faculty of MedicineJuntendo UniversityTokyoJapan
  4. 4.Faculty of EducationYamaguchi UniversityYamaguchiJapan

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