Functional Adaptation in Female Rats The Role of Estrogen Signaling 英文参考文献.docVIP

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Functional Adaptation in Female Rats The Role of Estrogen Signaling 英文参考文献.doc

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Functional Adaptation in Female Rats The Role of Estrogen Signaling 英文参考文献

FunctionalAdaptationinFemaleRats:TheRoleof EstrogenSignaling SusannahJ.Sample1,MollyA.Racette1,ZhenglingHao1,CathyF.Thomas2,MaryBehan2,PeterMuir1* 1Comparative Orthopaedic Research Laboratory, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America, 2DepartmentofComparativeBiosciences,SchoolofVeterinaryMedicine,UniversityofWisconsin-Madison,Madison,Wisconsin,UnitedStatesofAmerica Abstract Background: Sex steroids have direct effects on the skeleton. Estrogen acts on the skeleton via the classical genomic estrogen receptors alpha and beta (ERa and ERb), a membrane ER, and the non-genomic G-protein coupled estrogen receptor(GPER).GPERisdistributedthroughoutthenervoussystem,butlittleisknownaboutitseffectsonbone.Inmale rats,adaptationtoloadingisneuronallyregulated,butthishasnotbeenstudiedinfemales. Methodology/Principal Findings: Weused theratulnaend-loading modeltoinduceanadaptive modelingresponsein ovariectomized (OVX) female Sprague-Dawley rats. Rats were treated with a placebo, estrogen (17b-estradiol), or G-1, a GPER-specificagonist.FourteendaysafterOVX,ratsunderwentunilateralcyclicloadingoftherightulna;halfoftheratsin eachgrouphadbrachialplexusanesthesia(BPA)oftheloadedlimbbeforeloading.Tendaysafterloading,serumestrogen concentrations,dorsalrootganglion(DRG)geneexpressionofERa,ERb,GPER,CGRPa,TRPV1,TRPV4andTRPA1,andload- induced skeletal responses were quantified. We hypothesized that estrogen and G-1 treatment would influence skeletal responsestocyclicloadingthroughaneuronalmechanism.Wefoundthatestrogensuppressesperiostealboneformation infemalerats.ThisphysiologicaleffectisnotGPER-mediated.Wealsofoundthatabsolutemechanosensitivityinfemalerats wasdecreased,whencomparedwithmalerats.BlockingofadaptiveboneformationbyBPAinPlaceboOVXfemaleswas reduced. Conclusions:Estrogenactstodecreaseperiostealboneformationinfemaleratsinvivo.ThiseffectisnotGPER-mediated. Gender differences in absolute bone mechanosensitivity ex