胰岛素抵抗(insulin resistance,IR)与多囊卵巢综合征(polycystic ovary syndrome,PCOS)的发生发展有关,而与IR相关的胰岛素信号通路异常会引起卵巢局部代谢紊乱,进而影响卵泡发育及卵子质量。PCOS卵巢颗粒细胞中胰岛素作用的经典通路,包括磷脂酰肌醇3激酶(phosphoinositide 3-kinase,PI3K)/蛋白激酶B(protein kinase B,Akt)通路和丝裂原激活的蛋白激酶(mitogen-activated protein kinase,MAPK)/细胞外信号调节激酶(extracellular signal-regulated kinase,ERK)通路;与炎症相关的通路包括Toll样受体(Toll-like receptor,TLR)/核因子κB(nuclear factor-κB,NF-κB)通路等;氧化应激相关通路包括核转录因子红系2相关因子2(nuclear factor-erythroid 2-related factor 2,Nrf2)/血红素加氧酶-1(heme oxygenase-1,HO-1)途径和GTP酶免疫相关蛋白7(GTPase of immunity-associated protein 7,GIMAP7)/音猬因子(sonic hedgehog,SHH)途径;与脂质代谢相关的通路如激活转录因子4(activating transcription factor 4,ATF4)通路等。明确PCOS患者卵巢颗粒细胞中IR相关信号转导通路,增进PCOS病理生理机制的认识,进一步为PCOS的治疗提供新思路。
Pathways of Insulin Resistance in Ovarian Granulosa Cells of Polycystic Ovary Syndrome Patients
Insulin resistance(IR)is associated with the genesis and development of polycystic ovary syndrome(PCOS).The abnormity of insulin-related signaling pathways causes metabolism disorder,which affects follicle development and quality.In ovarian granulosa cells of PCOS,the classical pathways of insulin include phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)and mitogen-activated protein kinase(MAPK)/extracellular signal-regulated kinase(ERK).The pathways related with inflammation include Toll-like receptor(TLR)/nuclear factor-κB(NF-κB),and the pathways of oxidative stress include nuclear factor-erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)and GTPase of immunity-associated protein 7(GIMAP7)/sonic hedgehog(SHH).There are multiple pathways related with metabolism,such as the lipid metabolism-related pathway of activating transcription factor 4(ATF4).Therefore,clarifying the IR-related signal transduction pathway and molecular mechanism in ovarian granulosa cells of PCOS patients can supplement the knowledge of PCOS pathogenesis,and further provide new ideas for the treatment of PCOS.
Polycystic ovary syndromeInsulin resistanceIntracellular signaling peptides and proteinsSignal transductionGranulosa cells