Estrogen directly modulates circadian rhythms of PER2 expression in the uterus.
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 17beta-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.
Nakamura
Takahiro J
TJ
Department of Biology, University of Virginia, Charlottesville, Virginia, USA. tnakamura@mednet.ucla.edu
Sellix
Michael T
MT
Menaker
Michael
M
Block
Gene D
GD
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002940:Circadian Rhythm / Q000502:physiology*; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D066298:In Vitro Techniques; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010052:Ovariectomy; D056950:Period Circadian Proteins; D011374:Progesterone / Q000494:pharmacology; D020849:Raloxifene Hydrochloride / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014599:Uterus / Q000187:drug effects* / Q000378:metabolism
D018797:Cell Cycle Proteins; D004965:Estrogen Antagonists; D004967:Estrogens; D009687:Nuclear Proteins; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D020849:Raloxifene Hydrochloride; D011374:Progesterone; D004958:Estradiol; D008156:Luciferases