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

Eiko Iwahana, Ilia Karatsoreos, Shigenobu Shibata, Rae Silver*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

94 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)422-430
Number of pages9
JournalHormones and Behavior
Issue number3
Publication statusPublished - 2008 Mar


  • Androgen receptor
  • Circadian rhythms
  • Dihydrotestosterone
  • Gonadal hormones
  • Locomotor activity
  • Mouse
  • Testosterone

ASJC Scopus subject areas

  • Endocrinology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience


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