Sex differences in circadian timing systems: implications for disease
Open accessAbstract
Virtually every eukaryotic cell has an endogenous circadian clock and a biological sex. These cell-based clocks have been conceptualized as oscillators whose phase can be reset by internal signals such as hormones, and external cues such as light. The present review highlights the inter-relationship between circadian clocks and sex differences. In mammals, the suprachiasmatic nucleus (SCN) serves as a master clock synchronizing the phase of clocks throughout the body. Gonadal steroid receptors are expressed in almost every site that receives direct SCN input. Here we review sex differences in the circadian timing system in the hypothalamic-pituitary-gonadal axis (HPG), the hypothalamic-adrenal-pituitary (HPA) axis, and sleep-arousal systems. We also point to ways in which disruption of circadian rhythms within these systems differs in the sexes and is associated with dysfunction and disease. Understanding sex differentiated circadian timing systems can lead to improved treatment strategies for these conditions.
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Bottalico, L. N., & Weljie, A. M. (2020) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2020.113650 · Cited by 27 · see citing works
DePoy, L. M., Becker‐Krail, D. D., Zong, W., Petersen, K. A., Shah, N. M., Brandon, J. H., Miguelino, A. M., Tseng, G. C., Logan, R. W., & McClung, C. A. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.1830-20.2020 · Cited by 27 · see citing works
Regulation of Circadian Genes Nr1d1 and Nr1d2 in Sex-Different Manners during Liver Aging
Noh, S. G., Jung, H. J., Kim, S., Arulkumar, R., Kim, D. H., Park, D., & Chung, H. Y. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231710032 · Cited by 27 · see citing works
Circadian and kisspeptin regulation of the preovulatory surge
Piet, R. (2023) · Peptides · doi:10.1016/j.peptides.2023.170981 · Cited by 29 · see citing works
The Homeodomain Transcription Factors Vax1 and Six6 Are Required for SCN Development and Function
Pandolfi, E. C., Breuer, J. A., Huu, V. A. N., Talluri, T., Nguyen, D., Lee, J. S., Hu, R. J., Bharti, K., Skowronska‐Krawczyk, D., Gorman, M. R., et al. (2019) · Molecular Neurobiology · doi:10.1007/s12035-019-01781-9 · Cited by 26 · see citing works
Liang, X., Ding, Y., Zhu, X., Qiu, J., Shen, X., Xiong, Y., Zhou, J., Liang, X., & Xie, W. (2025) · Translational Psychiatry · doi:10.1038/s41398-025-03313-7 · Cited by 27 · see citing works
- Authors
- Bailey, M., & Silver, R.
- Affiliations
- Columbia University (US)
- Columbia University Irving Medical Center (US)
- Corresponding author
- Bailey, Matthew
- Silver, Rae
- ORCID
- Silver, Rae
- Venue
- Frontiers in Neuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 35
- Issue
- 1
- Pages
- 111-139
- ISSN
- 0091-3022 (ISSN-L)
- PMC
- PMC4041593
- OpenAlex
- W2089689504
- Cited by
- 348
- References
- 383
- Citations by year
- 2026: 21 · 2025: 41 · 2024: 36 · 2023: 35 · 2022: 39 · 2021: 39 · 2020: 34 · 2019: 20 · 2018: 18 · 2017: 14 · 2016: 24 · 2015: 18 · 2014: 9
- FWCI
- 2.02
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Frontiers in Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH075045, MH 075045)
- National Institute of Neurological Disorders and Stroke (NS-37919, R01NS037919)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- sex differences, circadian clock, suprachiasmatic nucleus, hypothalamic-pituitary-gonadal axis, hypothalamic-pituitary-adrenal axis, circadian rhythm disruption, circadian system, disease
- MeSH terms
- Animals, Circadian Rhythm, Humans, Hypothalamo-Hypophyseal System, Sex Characteristics, Sleep, Suprachiasmatic Nucleus
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