Estradiol enhances light-induced expression of transcription factors in the SCN
Abstract
The suprachiasmatic nucleus of the hypothalamus (SCN) is the master clock that regulates circadian and seasonal rhythms. Among these, the SCN regulates the phasic release of hormones and provides for the timing of the preovulatory luteinizing hormone (LH) surge necessary for ovulation in females. There is little evidence, however, of sex hormone effects on mechanisms underlying SCN function. This study examined the effects of exogenous administration of estradiol on the light-induced expression of transcription factors in the SCN of female rats. Ovariectomized (OVX) female rats were given estradiol or cholesterol implants and perfused 48 h later. Half of the animals were sacrificed 1 h after the regular onset of light within the colony. The rest had the lights go on 2 h prior to the regular time and perfused 1 h later. Collected brains were sliced and sets of SCN sections were processed for immunoreactivity (ir) detecting the Fos, pCREB, egr-1, CREB binding protein (CBP), and calbindin-D (28K) proteins. Following quantification, statistical analyses demonstrated that estradiol enhanced Fos and p-CREB-ir in the SCN of females that experienced a 2-h phase advance. The phase advance also enhanced calbindin and egr-1-ir, but the expression of these proteins was not affected by estradiol. These results demonstrate that estradiol enhances the levels of transcription factors that precede the expression of clock gene proteins in the SCN in response to advances in the onset of environmental light. These data support the hypothesis that steroid hormones play an important role in the fine tuning of the clock in the face of environmental changes in daylight.
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Both androgens and estrogens can activationally alter photic sensitivity within the entrainment pathway, as measured by the induction of FOS and clock genes (Per1, Per2).
“For example, both androgens and estrogens can activationally alter photic sensitivity within the entrainment pathway, as measured by the induction of immediate early gene expression (FOS) and clock genes (Per1, Per2, [3, 88, 90]).”
From The neuroendocrine control of the circadian system: Adolescent chronotype (2012) · cites this paper as [3]
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Melanopsin contributes to circadian photic responses in mice in a sex-dependent mannerPreprint
Miguel, K. C., Aranda, M. L., Bhoi, J. D., Diaz, M., Evans, J. A., & Schmidt, T. M. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.10.693461 · Cited by 1 · see citing works
Clemence, G. (2010) · theses.fr (ABES) · doi:10.70675/f4576f1dz0d59z4eb5z8f85zb207fb107180
Chen, X., Jiang, E., Yang, Y., Zhang, H., Liu, Z., Areb, E., Wang, Y., & Lan, X. (2026) · Biomolecules · doi:10.3390/biom16081201
- Authors
- Abizaid, A., Mezei, G., & Horvath, T. L.
- Affiliations
- Yale University (US)
- ORCID
- Abizaid, Alfonso
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2004-06
- Volume
- 1010
- Issue
- 1-2
- Pages
- 35-44
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2073873596
- Cited by
- 44
- References
- 69
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 1 · 2021: 1 · 2020: 5 · 2019: 1 · 2018: 1 · 2017: 2 · 2015: 1 · 2013: 3 · 2012: 2
- FWCI
- 0.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (R01MH059847, MH059847)
- 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
- estradiol, suprachiasmatic nucleus, circadian clock, light-induced gene expression, transcription factors, FOS, phosphorylated CREB, EGR1, CREB-binding protein, calbindin-D28k, phase advance, steroid hormones, clock gene expression, female rats
- MeSH terms
- Animals, Cholesterol, Circadian Rhythm, DNA-Binding Proteins, Estradiol, Female, Light, Nuclear Proteins, Ovariectomy, Photic Stimulation, Suprachiasmatic Nucleus, Transcription Factors, Trans-Activators, Up-Regulation, Proto-Oncogene Proteins c-fos, Rats, Sprague-Dawley, Cyclic AMP Response Element-Binding Protein, Immediate-Early Proteins, Estrous Cycle, CREB-Binding Protein, Rats, Early Growth Response Protein 1, Calbindins, S100 Calcium Binding Protein G
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