神经生物学 13、夏8 性与大脑-包爱民课件

大脑的性分化浙江大学医学部神经生物学系包爱民Offendersasapercentageofthepopulation:England&Wales2004Age(years)

%populationMalesFemalesAge17SocialTrends2006SexualDifferentiationoftheMammalianReproductiveSystem

FertilizationbyanXorYspermSexDeterminingRegionoftheYChromosome(SRY)leadstoproductionoftheTestisDeterminingFactorandtheformationofthetestesTherestofsexualdifferentiationdependson

1.Hormoneproductionbythetestis:Testosterone(whichmayleadtoformationofDihydrotestosteroneorEstradiol)andMullerianDuctInhibitingHormone. 2.Tissueresponsetoappropriatehormone.CurrentDogmaFig.11-3,p.328Differentiationofhumangenitals.

Themale’sSRYgene(Sex-determiningRegionY,SRY)causesthegonadtobecomeatestis,andthetestisproducestestosterone,whichmasculinizesdevelopment.Intheabsenceoftestosterone,developmentfollowsthefemalepattern.(Source:BasedonNetter,1983)AlexanderGM,HinesM.2002.Sexdifferencesinresponsetochildren'stoysinnonhumanprimates(Cercopithecusaethiopssabaeus).EvolutionandHumanBehavior23:467-479.肾上腺congenitaladrenalhyperplasia(CAH)Fig.11-12,p.342CAHgirlswereintermediatebetweenunaffectedgirlsandboys.Thesedatashowresultswhenthechildrenplayedalone.(Source:BasedondataofPasterskietal.,2005)IijimaM,ArisakaO,MinamotoF,AraiY.2001.Sexdifferencesinchildren'sfreedrawings:astudyongirlswithcongenitaladrenalhyperplasia.HormBehav40:99-104.IijimaM,ArisakaO,MinamotoF,AraiY.2001.Sexdifferencesinchildren'sfreedrawings:astudyongirlswithcongenitaladrenalhyperplasia.HormBehav40:99-104.腹股沟疝Thesexualdifferentiationofthegenitalstakesplacesmuchearlierindevelopment(hefirsttwomonthsofpregnancy)thansexualdifferentiationofthebrain(thatstartsinthesecondhalf

ofpregnancyandbecomesovertuponreachingadulthood),

thesetwoprocessesmaybeinfluencedindependently.

‘programming’or‘organizing’

effects(permanentmodification),and‘activating’effects(transientmodification)RatiosforwomenovermensufferingfromaselectionofneurologicalandpsychiatricdiseasesNote:abbreviations:REM=rapideyemovement

;ADHD=attentiondeficithyperactivitydisorder.(forreferencessee(Swaab2003))♂♀HofmanandSwaab,JAnat.1989;164:55-72.thesexuallydimorphicnucleusofthepreopticarea(SDN-POA).IsitNatureORNurture?Inthelate1950s/early1960stherewasawellacceptedconceptchampionedbyDr.JohnMoney:

HOWONEISRAISEDORREAREDFORABOUTTHEFIRSTTWOYEARSOFPOSTNATALLIFEISWHATDETERMINESONE’SPSYCHOSEXUALITY“Genderidentityissufficientlyincompletelydifferentiatedatbirthastopermitsuccessfulassignmentofageneticmaleasagirl.Genderidentitythendifferentiatesinkeepingwiththeexperienceofrearing---J.Money,1975Epispadias：尿道上裂；innominateosteotomy：骨盆切骨术ThreeChallengestotheNurtureHypothesisHormone-dependentsexualdifferentiationofbrainfunctionandstructurewellestablishedinlabanimals.Structuralsexdifferencesappeartoexistinthehumanbrainaswell.ThereportbyMoneywhichdemonstratedthemarkedeffectivenessofNurtureandactuallydictatedclinicalmanagementformorethan2decades,wasseriouslychallengedinthe1990s.EffectsofneonatalcastrationThenormaladultgonadalsteroidsEffectsofexogenoussteroidsNochangeFemaleCyclicLHreleaseFrequentlordosisNocyclicLHreleaseLordosisrareCyclicLHreleaseFrequentlordosisMaleNocyclicLHreleaseLordosisrareNochangeInfluenceoftheperinatalhormonalenvironmentonadultneuroendocrinefunctionintheratPotentialMechanismsStudiedSteroidsincreaseneuronalmitotic(有丝分裂)activity.

Nopositiveevidence,asyet.Steroidsalterapoptoticneuronaldeath. IntheSDN-POA,whichislargerinmalerats,Testosteronetreatmentsuppressesapoptoticneuronaldeath.-Butnottheonlymechanism!

SexualDifferentiationoftheRatBrainNature’s‘Blueprint’fortheinternalandexternalgenitaliaandthebrainisfemale.Amale’sbrainmustbeexposedtotesticularhormonesduringacriticalperiodofearlydevelopmenttoattainthemasculinecharacteristicsintermsofbrainstructureandfunction.Onemechanismforthealterationinbrainstructuremaybeanalterationinapoptosis.Theprocessofapoptosismaydefineonecriticalperiod.

PrenatalfactorsthatinfluencegenderidentitythatmayresultintranssexualityNote:abbreviations:CAH=congenitaladrenalhyperplasia;DES=diethylstilbestrolThebednucleusofthestriaterminalisSexdifferencesinBSTcofhumanbrainZhou,Hofman,Gooren,Swaab.Nature378:68-70,1995.Kruijveretal.J.Clin.Endocr.Metab.85:2034-2041,2000Fig.11-17,p.349Figure11.17:Volumesoftheinterstitialnucleus3oftheanteriorhypothalamus(INAH-3).Samplesarefemales(F),heterosexualmales(M),andhomosexualmales(HM).EachfilledcirclerepresentsapersonwhodiedofAIDS;eachtrianglerepresentsapersonwhodiedfromothercauses.TheoneopencirclerepresentsabisexualmanwhodiedofAIDS.(Source:Reprintedwithpermissionfrom“Adifferenceinhypothalamicstructurebetweenheterosexualandhomosexualmen,”byS.LeVay,Science,253,pp.1034–1037.Copyright©1991AmericanAssociationfortheAdvancementofScience.)Sexdifferencesin(INAH)-3ofhumanbrainPrenatalfactorsthatmayinfluencesexualorientationNote:abbreviations:CAH=congenitaladrenalhyperplasia;DES=diethylstilbestrol.Fig.11-14,p.346Sexualorientationsinadultrelativesofahomosexualmanorwoman.

Notethattheprobabilityofahomosexualorientationishighestamongmonozygotictwinsofahomosexualindividual,loweramongdizygotictwins,andstillloweramongadoptedbrothersorsisters.Thesedatasuggestageneticcontributiontowardthedevelopmentofsexualorientation.(Source:BasedonthedataofBailey&Pillard,1991;Bailey,Pillard,Neale,&Agyei,1993)Thereisapersistentlyoccurringgenomicmutation,sincehomosexualindividualsarelesslikelytohavechildrenAsufficientnumberofhomosexualsdohavechildrenwhichmaintainthegenesHe