胰岛素抵抗与多囊卵巢综合征.ppt

（优选）胰岛素抵抗与多囊卵巢综合征Figure2.Sectionofapolycysticovarywithmultiplesubscapularfollicularcystsandstromalhypertrophy(leftpanel).Athigherpower(x100)islandsofluteinizedthecacellsarevisibleinthestroma(rightpanel).Thismorphologicalchangeiscalledstromalhyperthecosisandappearstobedirectlycorrelatedwithcirculatinginsulinlevels.一、胰岛素与卵巢功能的关系胰岛素通过IGF-1受体刺激卵巢分泌雌激素，雄激素及
孕酮(细胞色素p-450c17α17α-羟化酶)
胰岛素抑制肝脏分泌SHBG雄激素的效应
胰岛素抑制肝脏合成IGFBP-1IGF-1的效应
同Gn相互作用
抑制卵泡的凋亡闭锁
上调IGF-1受体Figure1.PossibleMechanismsofInsulinStimulationofOvarianCytochromeP450c17ActivityandAndrogenproduction.Inthecacells,insulinmaydirectlystimulate(plussigns)ovariancytochromeP450c17,resultinginincreased17-hydroxylaseand,toalesserextent,17,20-lyaseactivity.Thiswouldleadtoincreasedproductionofandrostenedione,whichisthenconvertedtotestosteronebytheenzyme17-reductase.Alternativelyorinconjunctionwiththis,insulinmaystimulateovarianandrogenproductionindirectlybyenhancingtheamplitudeofserumluteinizinghormone(LH)pulses,andluteinizinghormonemaythenstimulateovariancytochromeP450c17activity.二、胰岛素抵抗与PCOS胰岛素及其受体的结构胰岛素的作用机理（1）FIG1.TheIRisaheterotetramerconsistingoftwoa,b-dimerslinkedbydisulfidebonds.Thea-subunitcontainstheligand-bindingsite,andtheb-subunitcontainsaligand-activatedtyrosinekinase.Tyrosineautophosphorylationincreasesthereceptor’styrosinekinaseactivitywhereasserinephosphorylationinhibitsit.胰岛素抵抗的机理(1)Figure9.Thetyrosine-phosphorylatedIRphosphorylatesintracellularsubstrates,suchasIRsubstrate(IRS)-1andIRS-2,initiatingsignaltransductionandtheplieotropicactionsofinsulin.TheactivationofPI3-K(PI3-kinase)bytyrosine-phosphorylatedIRS-1appearstobethepathwayforinsulin-mediatedglucosetransport.TheRas-MAPkinasepathwayappearstoregulatecellgrowthandglycogensynthesis.IR丝氨酸磷酸化因子
IR酪氨酸激酶抑制因子

膜糖蛋白PC-1/TNF-aFigure14.Insulinresistancein50%ofPCOSwomenappearstobesecondarytoacellmembrane-associatedfactor,presumablyaserine/threoninekinase,thatserine-phosphorylatestheIR-inhibitingsignaling.SerinephosphorylationofIRS-1appearstobethemechanismforTNF-medi