Selective Estrogen Receptor Down-Regulator and Selective Estrogen Receptor Modulators Differentially Regulate Lactotroph Proliferation 英文参考文献.docVIP

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Selective Estrogen Receptor Down-Regulator and Selective Estrogen Receptor Modulators Differentially Regulate Lactotroph Proliferation 英文参考文献.doc

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Selective Estrogen Receptor Down-Regulator and Selective Estrogen Receptor Modulators Differentially Regulate Lactotroph Proliferation 英文参考文献

SelectiveEstrogenReceptorDown-Regulatorand SelectiveEstrogenReceptorModulatorsDifferentially RegulateLactotrophProliferation SanjayKansra1,2,3*,ShenglinChen2,MadhaviLathaYadavBangaru2,LeightonSneade1,JosephA. Dunckley1,NiraBen-Jonathan1 1Department of Cancer and Cell Biology, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America, 2Department of Endocrinology, Metabolismand Clinical Nutrition, MedicalCollegeofWisconsin, Milwaukee,Wisconsin, United States ofAmerica, 3Department ofPharmacology,Medical College of Wisconsin,Milwaukee,Wisconsin,UnitedStatesofAmerica Abstract Background:Werecentlyreportedthatestrogenreceptora(ERa),eveninabsenceofestrogen(E2),playsacriticalrolein lactotroph homeostasis. The anti-estrogen ICI 182780 (ICI), but not tamoxifen or raloxifene, rapidly promoted the degradationofERa,andinhibitedcellproliferation.However,allthreeERantagonistssuppressedPRLrelease,suggesting thatreceptoroccupationissufficienttoinhibitprlgeneexpressionwhereasreceptordegradationisrequiredtosuppress lactotroph proliferation. In this study our objective was to determine whether ERa degradation versus occupation, differentiallymodulatesthebiologicaloutcomeofanti-estrogens. Principal Findings: Using the rat lactotroph cell line, GH3 cells, we report that ICI induced proteosome mediated degradationofERa.Incontrast,anERaspecificantagonist,MPP,thatdoesnotpromotedegradationofERa,didnotinhibit cellproliferation.Further,ICI,butnotMPP,abolishedanchorageindependentgrowthofGH3cells.Yet,bothICIandMPP wereequallyeffectiveinsuppressingprlexpressionandrelease,aswellasERE-mediatedtranscriptionalactivity. Conclusion: Taken together, our results demonstrate that in lactotrophs, ERa degradation results in decreased cell proliferation,whereasERaoccupationbyanantagonistthatdoesnotpromotedegradationofERaissufficienttoinhibitprl expression. Citation: Kansra S,Chen S, Bangaru MLY, Sneade L, Dunckley JA, et al.(2010) Selective Estrogen Receptor Down-Regulato