浅谈中枢性性早熟的发病机制  

Discussion on the Pathogenesis of Central Precocious Puberty

作　　者：倪娜 苏恒 孔祥阳 NI Na;SU Hen;KONG Xiang-Yang(Disease and Drug Genetics Laboratory,School of Medical,Kunming University of Science and Technology Medical College,Kunming 650000,China;The First People’s Hospital of Yunnan Province,Affiliated Hospital of Kunming University of Science and Technology,Kunming 650000,China)

机构地区：[1]昆明理工大学医学院疾病与药物遗传实验室,昆明650000 [2]昆明理工大学医学院附属医院云南省第一人民医院,昆明650000

出　　处：《中国生物化学与分子生物学报》2021年第6期727-732,共6页Chinese Journal of Biochemistry and Molecular Biology

摘　　要：性早熟(precocious puberty,PP)是一种常见的儿科性发育异常疾病。其中,中枢性性早熟(central precocious puberty,CPP)是由于下丘脑-垂体-性腺(hypothalamic-pituitary-gonadal,HPG)轴提前激活,导致促性腺激素的激素释放提前且大量释放,使性腺提前发育,青春期提前开始的疾病。青春期的发生受到基因和环境等因素的共同调控。目前的临床研究发现,KISS1基因的功能获得性突变、KISS1R即GPR54基因的功能丧失性突变、MKRN3环指印迹基因的功能丧失性突变,以及DLK1印迹基因的功能丧失性突变均是中枢性性早熟重要的单基因致病原因。KISS1基因是一种肿瘤转移抑制基因,KISS1R基因编码1个G蛋白偶联受体,该受体与其配体Kisspeptin形成GnRH分泌的兴奋性神经调节系统。它们在HPG轴的上游发挥作用。MKRN3基因是一种母系印迹基因,DLK1基因是一种调节细胞生长的基因,它们在HPG轴的下游发挥作用。近年来中枢性性早熟的发病率愈来愈高,这与社会经济的不断发展导致的环境内分泌干扰物(environmental endocrine disruptors,EEDs)的过多暴露有关。多项调查发现,儿童对环境内分泌干扰物的暴露程度与性早熟的发病率显著相关。而在人体中,这些内分泌干扰物也会影响肠道微生物的代谢。本文就目前中枢性性早熟的单基因致病机制、表观遗传修饰、肠道微生物以及环境因素等方面的研究展开综述,以期为该病的治疗和预防提供帮助。Precocious puberty(PP)is a common childhood sexual dysplasia.Central precocious puberty(CPP)is a disease in which the hypothalamic-pituitary-gonadal(HPG)axis is activated in early age,leading to the early release of gonadotrophin releasing hormone,the early development of gonads,and the early onset of puberty.The occurrence of puberty is regulated by gene and environment.Current clinical studies have found that gain-of-function mutations in the KISS1 gene,and loss-of-function mutations in KISS1R(also named GPR54),MKRN3 and DLK1 genes are all important single-gene causes of central precocious puberty.KISS1 is a tumor metastasis suppressor gene.KISS1R codes a G protein-coupled receptor which with its ligand,kisspeptin,forms an excitatory neuroregulator system for GnRH secretion.They play a role in the upstream of the HPG axis.MKRN3 is a maternal-imprinted gene.DLK1 is a gene that regulates the growth of cell.They play a role in the downstream of HPG axis.Recently,the incidence of central precocious puberty has become higher and higher,which is related to the excessive exposure of environmental endocrine disruptors(EEDs)due to the continuous development of social economy.A number of investigations have found that children’s exposure to EEDs is significantly related to the incidence of precocious puberty.In humans,these EEDs also affect the metabolism of gut microbes.This paper aims to review the current studies on the single-gene pathogenesis,epigenetics,gut microbiota and environmental factors of central precocious puberty,so as to provide help for the treatment and prevention of this disease.

关 键 词：表观遗传修饰 肠道微生物 环境内分泌干扰物 

分 类 号：Q341[生物学—遗传学]