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...

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Published in:American journal of physiology: endocrinology and metabolism 2008-11, Vol.295 (5), p.E1025-E1031
Main Authors: Nakamura, Takahiro J, Sellix, Michael T, Menaker, Michael, Block, Gene D
Format: Article
Language:English
Subjects:
Animals
Cell Cycle Proteins - genetics
Cell Cycle Proteins - metabolism
Circadian rhythm
Circadian Rhythm - physiology
Estradiol - pharmacology
Estrogen Antagonists - pharmacology
Estrogens
Estrogens - pharmacology
Female
Gene expression
Gene Expression Regulation - drug effects
In Vitro Techniques
Luciferases - genetics
Luciferases - metabolism
Mice
Mice, Transgenic
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Ovariectomy
Period Circadian Proteins
Progesterone
Progesterone - pharmacology
Raloxifene Hydrochloride - pharmacology
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
Reproductive system
Rodents
Suprachiasmatic Nucleus - drug effects
Suprachiasmatic Nucleus - metabolism
Transcription Factors - genetics
Transcription Factors - metabolism
Uterus - drug effects
Uterus - metabolism
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Summary: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 (E 2 ) on PER2::LUCIFERASE (PER2::LUC) expression in tissue explant cultures from ovariectomized PER2::LUC knockin mice. E 2 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 E 2 antagonist in uterine tissues, attenuated the effect of E 2 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 Address for reprint requests and other correspondence: T. J. Nakamura, Dept. of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience, Univ. of California Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90024-1759 (e-mail: tnakamura{at}mednet.ucla.edu )
ISSN:0193-1849
1522-1555
DOI:10.1152/ajpendo.90392.2008