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Cited by 127Circadian rhythm and melatoninHypothalamic control of reproductive hormonesSexual Differentiation and Disorders

Gonadectomy reveals sex differences in circadian rhythms and suprachiasmatic nucleus androgen receptors in mice

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Iwahana, Eiko, Karatsoreos, Ilia, Shibata, Shigenobu, Silver, Rae·2008·Hormones and Behavior
DOI 10.1016/j.yhbeh.2007.11.014PMC PMC3266066
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Abstract

In mammals, it is well established that circadian rhythms in physiology and behavior, including the rhythmic secretion of hormones, are regulated by a brain clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. While SCN regulation of gonadal hormone secretion has been amply studied, the mechanisms whereby steroid hormones affect circadian functions are less well known. This is surprising considering substantial evidence that sex hormones affect many aspects of circadian responses, and that there are significant sex differences in rhythmicity. Our previous finding that "core" and "shell" regions of the SCN differ in their expression of clock genes prompted us to examine the possibility that steroid receptors are localized to a specific compartment of the brain clock, with the discovery that the androgen receptor (AR) is concentrated in the SCN core in male mice. In the present study, we compare AR expression in female and male mice using Western blots and immunochemistry. Both of these methods indicate that ARs are more highly expressed in males than in females; gonadectomy eliminates and androgen treatment restores these sex differences. At the behavioral level, gonadectomy produces a dramatic loss of the evening activity onset bout in males, but has no such effect in females. Treatment with testosterone, or with the non-aromatizable androgen dihydrotestosterone, restores male locomotor activity and eliminates sex differences in the behavioral response. The results indicate that androgenic hormones regulate circadian responses, and suggest an SCN site of action.

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Crossref · 10.1016/j.yhbeh.2007.11.014

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  • 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 [78]

  • Ovariectomized adult female rodents lost the phase advance and increase in wheel running activity that typically accompanies estrus, and in general exhibited a more dispersed activity distribution and delayed activity rhythm phase.

    “This was also true of ovariectomized adult female rodents: they lost the phase advance and increase in wheel running activity that typically accompanies estrus [49, 78, 100, 129], and in general exhibited a more dispersed activity distribution and delayed activity rhythm phase [187, 203, although see 23].”

    From The neuroendocrine control of the circadian system: Adolescent chronotype (2012) · cites this paper as [78]

  • 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 [78]

  • Both androgens and estrogens can consolidate rhythms at the beginning of the active period in rodents.

    “This conclusion is consistent with previous data indicating that both androgens and estrogens can consolidate rhythms at the beginning of the active period in rodents [78, 128, 187, 203]”

    From The neuroendocrine control of the circadian system: Adolescent chronotype (2012) · cites this paper as [78]

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Authors
Iwahana, E., Karatsoreos, I., Shibata, S., & Silver, R.
Affiliations
  • Waseda University (JP)
  • Columbia University (US)
Corresponding author
Silver, Rae
ORCID
Venue
Hormones and Behavior
Publisher
Elsevier BV
Published
2008-03
Volume
53
Issue
3
Pages
422-430
ISSN
0018-506X (ISSN-L)
DOI
10.1016/j.yhbeh.2007.11.014
PMC
PMC3266066
OpenAlex
W2084979196
Cited by
127
References
55
Citations by year
2026: 4 · 2025: 12 · 2024: 7 · 2023: 6 · 2022: 12 · 2021: 8 · 2020: 4 · 2019: 8 · 2018: 6 · 2017: 8 · 2016: 3 · 2015: 7 · 2014: 7 · 2013: 10 · 2012: 4
FWCI
1.77
Type
journal article
Language
en
Open access
Licence
Locations
  • Hormones and Behavior (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • Natural Sciences and Engineering Research Council of Canada
  • Japan Society for the Promotion of Science
  • 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 › Molecular Biology › Sexual Differentiation and Disorders
Keywords
gonadectomy, sex differences, circadian rhythm, suprachiasmatic nucleus, androgen receptor, androgens, testosterone, dihydrotestosterone, locomotor activity, clock genes, hypothalamus
MeSH terms
Analysis of Variance, Animals, Biological Clocks, Circadian Rhythm, Female, Gonads, Male, Motor Activity, Receptors, Androgen, Sex Characteristics, Suprachiasmatic Nucleus, Testosterone, Mice

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