title: Estradiol enhances light-induced expression of transcription factors in the SCN.
abstract: The suprachiasmatic nucleus of the hypothalamus (SCN) is the master clock that regulates circadian and seasonal rhythms. Among these, the SCN regulates the phasic release of hormones and provides for the timing of the preovulatory luteinizing hormone (LH) surge necessary for ovulation in females. There is little evidence, however, of sex hormone effects on mechanisms underlying SCN function. This study examined the effects of exogenous administration of estradiol on the light-induced expression of transcription factors in the SCN of female rats. Ovariectomized (OVX) female rats were given estradiol or cholesterol implants and perfused 48 h later. Half of the animals were sacrificed 1 h after the regular onset of light within the colony. The rest had the lights go on 2 h prior to the regular time and perfused 1 h later. Collected brains were sliced and sets of SCN sections were processed for immunoreactivity (ir) detecting the Fos, pCREB, egr-1, CREB binding protein (CBP), and calbindin-D (28K) proteins. Following quantification, statistical analyses demonstrated that estradiol enhanced Fos and p-CREB-ir in the SCN of females that experienced a 2-h phase advance. The phase advance also enhanced calbindin and egr-1-ir, but the expression of these proteins was not affected by estradiol. These results demonstrate that estradiol enhances the levels of transcription factors that precede the expression of clock gene proteins in the SCN in response to advances in the onset of environmental light. These data support the hypothesis that steroid hormones play an important role in the fine tuning of the clock in the face of environmental changes in daylight.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Abizaid
authors.forename: Gabor
authors.initials: G
authors.lastname: Mezei
authors.forename: Tamas L
authors.initials: TL
authors.lastname: Horvath
mesh_terms: D000818:Animals; D050882:CREB-Binding Protein; D064026:Calbindins; D002784:Cholesterol / Q000494:pharmacology; D002940:Circadian Rhythm / Q000187:drug effects / Q000235:genetics*; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D051766:Early Growth Response Protein 1; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D030762:Estrous Cycle / Q000187:drug effects / Q000235:genetics*; D005260:Female; D017874:Immediate-Early Proteins / Q000187:drug effects / Q000378:metabolism; D008027:Light; D009687:Nuclear Proteins / Q000187:drug effects / Q000378:metabolism; D010052:Ovariectomy; D010775:Photic Stimulation; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D064030:S100 Calcium Binding Protein G / Q000187:drug effects / Q000378:metabolism; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015534:Trans-Activators / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D064026:Calbindins; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; D016760:Proto-Oncogene Proteins c-fos; D064030:S100 Calcium Binding Protein G; D015534:Trans-Activators; D014157:Transcription Factors; D004958:Estradiol; D002784:Cholesterol; D050882:CREB-Binding Protein; C494365:Crebbp protein, rat