Pubertal hormones alter circadian timekeeping: Evidence from two rodent models, Rattus norvegicus and Octodon degus.

Abstract

There is overwhelming evidence that the circadian timekeeping system is sensitive to gonadal hormones during perinatal development and adulthood. However, there is a noticeable lack of research in animal models focusing on circadian rhythms during puberty, a developmental window of dramatic hormonal change. This dissertation addresses this research gap using experiments in both fast-developing and slow-developing rodent species (Rattus norvegicus and Octodon degus).

The results indicate that the circadian system continues to develop across the post-weaning and pubertal periods in both species in a manner that exhibits strong sex differences. In males, pubertal changes in activity rhythms were robust, involving a switch from bimodal to unimodal activity patterns as well as a 3-5 hr magnitude phase-advance of activity rhythms relative to the environmental light-dark cycle. Pre-pubertal gonadectomy diminished these changes in both species, indicating that pubertal hormones were involved in producing the changes. Overall, females showed smaller circadian phase changes than males during puberty. In the degu, these sex differences were extreme, with female degus almost completely lacking phase changes during puberty.

Results suggest that pubertal hormones could act on multiple components of the circadian system. For example, preliminary data from the degu suggest that a photosensitive rhythmic component of the central circadian oscillator (Per1) exhibits phase changes during puberty that parallel phase changes in behavioral rhythms. However, pubertal rats exhibited a reorganization of activity rhythms under constant conditions, independent of photic entrainment. Thus, both the photic entrainment pathway and downstream circadian elements may be altered during puberty.

Taken in tandem with growing evidence from multiple species, as well as sleep electrophysiological studies from our own lab, it appears that the processes governing daily sleep and activity rhythms continue to develop far into the pubertal period in many mammals. This conclusion is discussed in the context of the developmental ecology of these rodent species. The ramifications of these results for the wide-spread use of young animals by the scientific community for patch-clamp experiments of the circadian system are also discussed. Finally, this evidence can inform the national debate regarding teenage sleep patterns and high school start times.