The etiology of central precocious puberty (CPP) is multiple and heterogeneous, including congenital and acquired causes that can be associated with structural or functional brain alterations. All causes of CPP culminate in the premature pulsatile secretion of hypothalamic GnRH and, consequently, in the premature reactivation of hypothalamic-pituitary-gonadal axis. The activation of excitatory factors or suppression of inhibitory factors during childhood represent the 2 major mechanisms of CPP, revealing a delicate balance of these opposing neuronal pathways. Hypothalamic hamartoma (HH) is the most well-known congenital cause of CPP with central nervous system abnormalities. Several mechanisms by which hamartoma causes CPP have been proposed, including an anatomical connection to the anterior hypothalamus, autonomous neuroendocrine activity in GnRH neurons, trophic factors secreted by HH, and mechanical pressure applied to the hypothalamus. The importance of genetic and/or epigenetic factors in the underlying mechanisms of CPP has grown significantly in the last decade, as demonstrated by the evidence of genetic abnormalities in hypothalamic structural lesions (eg, hamartomas, gliomas), syndromic disorders associated with CPP (Temple, Prader-Willi, Silver-Russell, and Rett syndromes), and isolated CPP from monogenic defects (MKRN3 and DLK1 loss-of-function mutations). Genetic and epigenetic discoveries involving the etiology of CPP have had influence on the diagnosis and familial counseling providing bases for potential prevention of premature sexual development and new treatment targets in the future. Global preventive actions inducing healthy lifestyle habits and less exposure to endocrine-disrupting chemicals during the lifespan are desirable because they are potentially associated with CPP.

中文翻译：

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中枢性性早熟病因学中涉及的先天性和后天性机制。

中枢性性早熟（CPP）的病因多种多样且异质，包括可能与大脑结构或功能改变相关的先天性和后天性原因。CPP 的所有原因都会导致下丘脑 GnRH 过早脉动性分泌，从而导致下丘脑-垂体-性腺轴过早重新激活。儿童时期兴奋性因子的激活或抑制性因子的抑制代表了 CPP 的 2 个主要机制，揭示了这些对立神经元通路的微妙平衡。下丘脑错构瘤 (HH) 是导致中枢神经系统异常的 CPP 的最常见的先天性原因。错构瘤引起 CPP 的几种机制已被提出，包括与下丘脑前部的解剖学联系、GnRH 神经元的自主神经内分泌活动、HH 分泌的营养因子以及施加到下丘脑的机械压力。遗传和/或表观遗传因素在 CPP 潜在机制中的重要性在过去十年中显着增长，下丘脑结构性病变（例如错构瘤、神经胶质瘤）、与 CPP 相关的综合征性疾病的遗传异常证据证明了这一点（Temple 、Prader-Willi、Silver-Russell 和 Rett 综合征），并从单基因缺陷（MKRN3 和 DLK1 功能丧失突变）中分离出 CPP。涉及 CPP 病因的遗传和表观遗传发现对诊断和家庭咨询产生了影响，为潜在预防性发育早熟和未来新的治疗目标提供了基础。需要采取全球预防措施，养成健康的生活习惯，并在生命周期内减少接触内分泌干扰性化学物质，因为它们可能与 CPP 有关。