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1、Estrogens,Progestins,&HormoneTherapyLoreleiVandiverChem5398March25,2008OutlineEstrogensHistorySynthesisReceptorsMedicalUsesProgestinsHistorySynthesisReceptorsMedicalUsesHormoneTherapyMenopauseTypesofHTSteroidSynthesisPicturetakenfromwikipedia.comEstrogensRolesinbothmalesandfemalesMales:growthsp
2、urt,skeletalmaturation,epiphysealclosure,maturationofsperm.Females:developmentoffemalesexorgansandsecondarysexcharacteristics,regulatemenstrualcycle,skeletalmaturationThemostprevalentformsofhumanestrogenareestradiolandestrone.Bothareproducedandsecretedbytheovaries,althoughestroneisalsomadeinthe
3、adrenalglandsandotherorgans.EstrogenHistory1900:Knauerfoundthatovariantransplantspreventsymptomsofgonadectomy.1923:AllenandDoisydevisedabioassayforovarianextracts.1925:Frankandassociatesdetectedanactivesexprincipleinthebloodofsows.1926:LoeweandLangediscoveredthatafemalesexhomonevariedthroughout
4、menstrualcycle.1928:Zondekreportedexcretionofestrogenduringpregnancy.1929:EstrogencrystallizebyButenandtandDoisy1941:FDAapprovalofestrogentherapyformenopausalsymptoms.EstrogenSynthesis-inthebodySynthesisofestrogensmainlyintheovary,bythesynthesisofandrostenedionefromcholesterol.Androstenedioneis
5、thenconvertedtoestroneorestradiol,eitherimmediatelyorthroughtestosterone.Thisprocessiscatalyzedbytheenzymearomatase.EstradiolEstriolEstroneTestosteroneAndrostenedioneAromataseAromataseEstrogenReceptorsEstrogensactassignalingmoleculesbyinteractingwithspecifictargetcells.Includetissuesofthebreast
6、,uterus,brain,heart,liver,andbone.Thesetargetcellshavebindingsitescalledestrogenreceptors.Therearetwoestrogenreceptorsthatarenormallyfoundinthecell’snucleus:ERαandERβ.EstrogenReceptorscont.Thereceptorchangesconformationduetothedissociationofheatshockproteinsafterestrogenbindstoit.Thereceptorund
7、ergoesdimerizationinorderforincreasedaffinitytoDNA.Thisestrogen-receptorcomplexcannowbindtospecificDNAsites,calledestrogenresponseelements(EREs).GenesareactivatedtoproducemessengerRNA,whichguidethesynthesisofnewproteins,determined
