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Cited by 136Circadian rhythm and melatoninHypothalamic control of reproductive hormonesSleep and Wakefulness Research

A role for androgens in regulating circadian behavior and the suprachiasmatic nucleus

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Karatsoreos, Ilia N., Wang, Alice, Sasanian, Jasmine, Silver, Rae·2007·Endocrinology
DOI 10.1210/en.2007-0775PMC PMC3281763
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Abstract

The suprachiasmatic nucleus (SCN) of the hypothalamus is the locus of a master circadian clock controlling behavioral and physiological rhythms, including rhythmic secretion of gonadal hormones. Gonadectomy results in marked alteration of circadian behaviors, including lengthened free-running period, decreased precision of daily onset of running, and elimination of early-evening but not late-night activity bouts. Androgen replacement restores these responses. These aspects of rhythmicity are thought to be regulated by the brain clock, although the site of androgen action remains unknown. Anatomically, the rodent SCN is composed of a ventrolateral core and a dorsomedial shell, and the present studies show that androgen receptors (AR) are localized to the ventrolateral core SCN. Using a transgenic mouse bearing dual reporter molecules driven by the AR targeted to both membrane and nucleus, we find that projections of AR-containing cells form a dense plexus in the core, with their fibers appearing to exit the SCN dorsally. In a second transgenic strain, in which the retinorecipient gastrin-releasing peptide cells express a green fluorescent protein reporter, we show that gastrin-releasing peptide cells contain AR. Through immunocytochemistry, we also show that SCN AR cells express FOS after a light pulse. Importantly, gonadectomy reduces the FOS response after a phase-shifting light pulse, whereas androgen replacement restores levels to those in intact animals. Taken together, the results support previous findings of a hypothalamic neuroendocrine feedback loop. As such, the SCN regulates circadian rhythms in gonadal hormone secretion, and in turn, androgens act on their receptors within the SCN to alter circadian function.

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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 [90]

  • In adult laboratory rodents, a wide variety of gonadal hormones can affect the phase of circadian rhythms.

    “Indeed, in adult laboratory rodents a wide variety of gonadal hormones can affect the phase of circadian rhythms, including estrogens, progestins, androgens, and non-traditional neuroactive steroids (e.g., rats: [8, 17], hamsters: [49, 51, 129], mice: [23, 47, 78, 90], degus: [80, 100]).”

    From The neuroendocrine control of the circadian system: Adolescent chronotype (2012) · cites this paper as [90]

  • Administration of testosterone or dihydrotestosterone to castrated adult males restored normal circadian activity patterns, and estrogen treatment reconsolidated rhythms in ovariectomized rats.

    “In these previous studies, the administration of testosterone or dihydrotestosterone to castrated adult males was able to restore the normal circadian activity patterns [47, 78, 90, 128] and estrogen treatment was able to reconsolidate rhythms in ovariectomized rats [187, 203].”

    From The neuroendocrine control of the circadian system: Adolescent chronotype (2012) · cites this paper as [90]

  • Gonadal hormones are already known to have species-specific effects during adulthood.

    “This would not be an unprecedented conclusion, as gonadal hormones are already known to have species-specific effects during adulthood.”

    From The neuroendocrine control of the circadian system: Adolescent chronotype (2012) · cites this paper as [90]

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Authors
Karatsoreos, I. N., Wang, A., Sasanian, J., & Silver, R.
Affiliations
  • Columbia University (US)
  • Barnard College (US)
ORCID
Venue
Endocrinology
Publisher
The Endocrine Society
Published
2007-11-01
Volume
148
Issue
11
Pages
5487-5495
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
DOI
10.1210/en.2007-0775
PMC
PMC3281763
OpenAlex
W2161296727
Cited by
136
References
63
Citations by year
2026: 6 · 2025: 13 · 2024: 8 · 2023: 3 · 2022: 13 · 2021: 6 · 2020: 11 · 2019: 5 · 2018: 3 · 2017: 1 · 2016: 3 · 2015: 7 · 2014: 7 · 2013: 9 · 2012: 9
FWCI
3.13
Type
journal article
Language
en
Open access
Locations
  • Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
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 › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
Keywords
androgens, suprachiasmatic nucleus, circadian rhythm, androgen receptor, gonadectomy, androgen replacement, free-running period, activity rhythms, Fos expression, light pulses, phase shift, transgenic reporter mice
MeSH terms
Androgens, Animals, Behavior, Animal, Cell Count, Circadian Rhythm, Male, Mice, Inbred C57BL, Mice, Transgenic, Models, Biological, Motor Activity, Neurons, Orchiectomy, Receptors, Androgen, Dihydrotestosterone, Suprachiasmatic Nucleus, Testosterone, Mice

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