Changes in circadian rhythms during puberty in Rattus norvegicus: Developmental time course and gonadal dependency
Open accessAbstract
During puberty, humans develop a later chronotype, exhibiting a phase-delayed daily rest/activity rhythm. The purpose of this study was to determine: 1) whether similar changes in chronotype occur during puberty in a laboratory rodent species, 2) whether these changes are due to pubertal hormones affecting the circadian timekeeping system. We tracked the phasing and distribution of wheel-running activity rhythms during post-weaning development in rats that were gonadectomized before puberty or left intact. We found that intact peripubertal rats had activity rhythms that were phase-delayed relative to adults. Young rats also exhibited a bimodal nocturnal activity distribution. As puberty progressed, bimodality diminished and late-night activity phase-advanced until it consolidated with early-night activity. By late puberty, intact rats showed a strong, unimodal rhythm that peaked at the beginning of the night. These pubertal changes in circadian phase were more pronounced in males than females. Increases in gonadal hormones during puberty partially accounted for these changes, as rats that were gonadectomized before puberty demonstrated smaller phase changes than intact rats and maintained ultradian rhythms into adulthood. We investigated the role of photic entrainment by comparing circadian development under constant and entrained conditions. We found that the period (τ) of free-running rhythms developed sex differences during puberty. These changes in τ did not account for pubertal changes in entrained circadian phase, as the consolidation of activity at the beginning of the subjective night persisted under constant conditions in both sexes. We conclude that the circadian system continues to develop in a hormone-sensitive manner during puberty.
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Circulating androgen levels are critical for some of the behaviors assessed.
“Because circulating androgen levels are critical for some of these behaviors, the apparent lack of treatment effects was somewhat surprising.”
From Developmental Treatment with Ethinyl Estradiol, but Not Bisphenol A, Causes Alterations in Sexually Dimorphic Behaviors in Male and Female Sprague Dawley Rats (2014) · cites this paper as Hagenauer et al., 2011
The Discussion reports that pubertal changes in rat circadian activity depend on gonadal hormones. It says increasing testosterone may contribute to the male activity pattern, but does not establish that circulating androgen levels are critical for the behaviors assessed. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe necessity of normal circulating levels of testosterone or estradiol for sex-typical running wheel activity is evident from the effects of adult or preweaning castration and/or exogenous replacement.
“For example, the necessity of normal circulating levels of testosterone or estradiol for sex-typical running wheel activity is clearly evident from the effects caused by adult or preweaning castration and/or exogenous replacement (Hagenauer et al., 2011;Ibebunjo et al., 2011;Jackson et al., 2011;Rivera and Eckel, 2005).”
From Developmental Treatment with Ethinyl Estradiol, but Not Bisphenol A, Causes Alterations in Sexually Dimorphic Behaviors in Male and Female Sprague Dawley Rats (2014) · cites this paper as Hagenauer et al., 2011
The Results (Experiment 1, Mean Activity) report that prepubertal gonadectomy reduced wheel-running activity, especially in females. The Discussion also describes adult gonadectomy and hormone-replacement findings from previous studies. But it presents the role of increasing estrogen in the pubertal change as likely, rather than establishing that normal circulating levels of both hormones are necessary for sex-typical activity. (LLM, conf=0.82)
Experimental — accuracy not yet measuredGonadectomized animals either completely lacked a shift in chronotype during the normal pubertal period (degus) or showed a much diminished shift (rats).
“We found that gonadectomized animals either completely lacked a shift in chronotype during the normal pubertal period (degus: [67, 75]) or showed a much diminished shift in chronotype (rats: [66]).”
From The neuroendocrine control of the circadian system: Adolescent chronotype (2012) · cites this paper as [66]
The pubertal shift in rest/activity rhythms in rodents is similar to that in human adolescents.
“This meant that, overall, both rodent species showed a large (2-4) hr shift in the phasing of their rest/activity rhythms during pubertal development, similar to human adolescents (Figure 2C-D, [66-67, 75, 114, 185]).”
From The neuroendocrine control of the circadian system: Adolescent chronotype (2012) · cites this paper as [66]
In rats, males showed a larger shift in the phasing of rest/activity rhythms during puberty than females.
“For rats, males showed a larger shift in the phasing of rest/activity rhythms during puberty than females [66].”
From The neuroendocrine control of the circadian system: Adolescent chronotype (2012) · cites this paper as [66]
The developmental timing for the chronotype changes in rats differed by sex, paralleling sex differences in the progression through puberty.
“Similar to humans, the developmental timing for the chronotype changes in rats also differed by sex, paralleling sex differences in the progression through puberty [66].”
From The neuroendocrine control of the circadian system: Adolescent chronotype (2012) · cites this paper as [66]
Pubertal changes in the distribution of activity were internally-generated and not a change in the passive response of the animals to the light cycle.
“These data suggested that pubertal changes in the distribution of activity were internally-generated and not a change in the passive response of the animals to the light cycle [66].”
From The neuroendocrine control of the circadian system: Adolescent chronotype (2012) · cites this paper as [66]
Both rodent species showed a large (2-4) hr shift in the phasing of their rest/activity rhythms during pubertal development.
“This meant that, overall, both rodent species showed a large (2-4) hr shift in the phasing of their rest/activity rhythms during pubertal development, similar to human adolescents (Figure 2C-D, [66-67, 75, 114, 185]).”
From The neuroendocrine control of the circadian system: Adolescent chronotype (2012) · cites this paper as [66]
In both rat studies, the free-running period of male and female rats was closest to 24 h during the youngest developmental time point, immediately after placement into constant conditions.
“In both of the rat studies [66, 114], the free-running period of the male and female rats was closest to 24 h during the youngest developmental time point, immediately after placement into constant conditions.”
From The neuroendocrine control of the circadian system: Adolescent chronotype (2012) · cites this paper as [66]
These changes in free-running period do not predict the pubertal change in chronotype, which takes the form of a phase-advance in both sexes.
“Thus, these changes in free-running period do not predict the pubertal change in chronotype, which takes the form of a phase-advance in both sexes [66].”
From The neuroendocrine control of the circadian system: Adolescent chronotype (2012) · cites this paper as [66]
Two studies in laboratory rats also revealed a change in free-running period around the time of puberty.
“Two studies in laboratory rats also revealed a change in free-running period around the time of puberty [66, 114].”
From The neuroendocrine control of the circadian system: Adolescent chronotype (2012) · cites this paper as [66]
In rats, the increase in the amplitude of rest/activity rhythms during puberty is particularly notable and strongly related to pubertal hormones: prepubertal gonadectomy prevents activity levels from increasing much beyond prepubertal levels in both males and females.
“In rats, the increase in the amplitude of rest/activity rhythms during puberty is particularly notable and strongly related to pubertal hormones: prepubertal gonadectomy prevents activity levels from increasing much beyond prepubertal levels in both males and females [66].”
From The neuroendocrine control of the circadian system: Adolescent chronotype (2012) · cites this paper as [66]
A change in the sensitivity of the circadian system to light cannot be solely responsible for the shift in chronotype observed in our animals, because reorganization of rest/activity rhythms during puberty was observed even under conditions of constant darkness.
“We believe that a change in the sensitivity of the circadian system to light cannot be solely responsible for the shift in chronotype observed in our animals, because we observed a reorganization of rest/activity rhythms during puberty even under conditions of constant darkness [66].”
From The neuroendocrine control of the circadian system: Adolescent chronotype (2012) · cites this paper as [66]
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- Authors
- Hagenauer, M. H., King, A. F., Possidente, B., McGinnis, M. Y., Lumia, A. R., Peckham, E. M., & Lee, T. M.
- Affiliations
- University of Michigan (US)
- Skidmore College (US)
- The University of Texas at San Antonio Health Science Center (US)
- Corresponding author
- Hagenauer, Megan Hastings
- Venue
- Hormones and Behavior
- Publisher
- Elsevier BV
- Published
- 2011-06
- Volume
- 60
- Issue
- 1
- Pages
- 46-57
- ISSN
- 0018-506X (ISSN-L)
- PMC
- PMC3112245
- OpenAlex
- W2137783991
- Cited by
- 43
- References
- 20
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 5 · 2021: 6 · 2020: 2 · 2019: 3 · 2017: 3 · 2016: 4 · 2015: 5 · 2014: 2 · 2013: 6 · 2012: 3
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hormones and Behavior (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Science Foundation
- University of Michigan
- National Heart, Lung, and Blood Institute (R01HL061667)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32 HD 07048, T32HD007048)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Keywords
- puberty, circadian rhythm, chronotype, circadian phase delay, gonadal hormones, gonadectomy, sex differences, ultradian rhythms, bimodal activity, free-running period, light entrainment, wheel running, Rattus norvegicus, post-weaning development
- MeSH terms
- Animals, Castration, Circadian Rhythm, Female, Gonads, Male, Running, Sex Factors, Sexual Maturation, Rats
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