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This Article Full Text Full Text (PDF) All Versions of this Article: 295/5/E1025    most recent 90392.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Nakamura, T. J. Articles by Block, G. D. Search for Related Content PubMed PubMed Citation Articles by Nakamura, T. J. Articles by Block, G. D.

Estrogen directly modulates circadian rhythms of PER2 expression in the uterus

Department of Biology, University of Virginia, Charlottesville, Virginia

Submitted 24 April 2008 ; accepted in final form 24 August 2008

Fluctuations in circulating estrogen and progesterone levels associated with the estrous cycle alter circadian rhythms of physiology and behavior in female rodents. Endogenously applied estrogen shortens the period of the locomotor activity rhythm in rodents. We recently found that estrogen implants affect Period (Per) gene expression in the suprachiasmatic nucleus (SCN; central clock) and uterus of rats in vivo. To explore whether estrogen directly influences the circadian clock in the SCN and/or tissues of the reproductive system, we examined the effects of 17β-estradiol (E₂) on PER2::LUCIFERASE (PER2::LUC) expression in tissue explant cultures from ovariectomized PER2::LUC knockin mice. E₂ applied to explanted cultures shortened the period of rhythmic PER2::LUC expression in the uterus but did not change the period of PER2::LUC expression in the SCN. Raloxifene, a selective estrogen receptor modulator and known E₂ antagonist in uterine tissues, attenuated the effect of E₂ on the period of the PER2::LUC rhythm in the uterus. These data indicate that estrogen directly affects the timing of the molecular clock in the uterus via an estrogen receptor-mediated response.

ovarian steroid hormone; period; PER2::LUCIFERASE; raloxifene; suprachiasmatic nucleus

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