Effects of testosterone on circadian rhythmicity in old mice

  • Atsuyoshi Hashimoto
  • Shingo Fujiki
  • Wataru Nakamura
  • Takahiro J. NakamuraEmail author
Original Paper


Serum testosterone concentration decreases with age in humans and rodents. Accordingly, old male mice show changes in locomotor activity rhythms: a lengthened free-running period and decreased activity levels among others. To investigate whether testosterone replacement improves the age-related decline in circadian rhythmicity, we examined the effects of testosterone on the circadian rhythms of wheel running activity in old male mice. Intact male C57BL/6J mice (18–22 months old) were subcutaneously implanted with silicone tubes packed with testosterone propionate (TP) or cholesterol. TP treatment significantly decreased the daily wheel running revolutions in a normal light/dark (LD) cycle and in constant darkness (DD), but did not affect the free-running period. The same experiment performed on young male gonadectomized mice (3–5 months old) demonstrated that TP treatment significantly increased activity levels in both LD and DD. These results suggest that testosterone replacement exacerbates the age-related decline in circadian rhythmicity.


Circadian rhythm Testosterone Wheel running Free-running period PER2::LUC 


Author contributions

WN and TJN designed the study; SF, AH, and TJN performed the experiments; SF, AH, and TJN analyzed the data; WN and TJN wrote the paper.


This work was supported by JSPS KAKENHI Grant numbers 17H04022.

Compliance with ethical standards

Conflict of interest

The authors have nothing to disclose.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. The protocol was approved by the Institutional Animal Care and Use Committee at the School of Agriculture, Meiji University.


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Copyright information

© The Physiological Society of Japan and Springer Japan KK, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Laboratory of Animal Physiology, School of AgricultureMeiji UniversityKawasakiJapan
  2. 2.Department of Oral-Chrono Physiology, Graduate School of Biomedical SciencesNagasaki UniversityNagasakiJapan

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