Effects of testosterone on circadian rhythmicity in old mice
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.
KeywordsCircadian rhythm Testosterone Wheel running Free-running period PER2::LUC
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.
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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