Table_1_Initiation of the Hypothalamic–Pituitary–Gonadal Axis in Young Girls Undergoing Central Precocious Puberty Exerts Remodeling Effects on the Prefrontal Cortex.docx

Central precocious puberty (CPP) has been shown to exert significant effects on psychosocial development. These early puberty-related hormones and psychosocial functional changes are considered to be associated with specific brain development. However, the biological mechanisms underlying the sculpting of human brain architecture and modulation of psychosocial transformation by puberty-related hormonal maturation remain elusive, especially during the early phase of CPP. The current investigation aims to specify the brain regions in which early hormone-related maturation effects occur during CPP and their relationships with psychological functions. 65 young girls (aged 4.3–8.0 years) underwent structural imaging on a 3T MR system, completed psychological tests and performed the gonadotropin-releasing hormone (GnRH) stimulation test to identify hormonal manifestations of hypothalamic–pituitary–gonadal axis (HPG axis) activation. Based on the GnRH test, 28 young girls were identified with CPP, whereas the other 37 girls were identified with non-central precocious puberty (NCPP). Cortical parameters were calculated and compared between the two groups after adjusting for age, weight, and height. Brain regions showing group differences were extracted and correlated with serum hormone levels and psychological parameters. The CPP girls showed thinner cortices primarily in the right rostral middle frontal cortex. This morphological difference was positively correlated with stimulated estradiol (E2) levels. Further, higher E2 levels were significantly associated with higher hyperactivity scores. Premature HPG axis activation in CPP girls at an early stage appears to exert remodeling effects on brain anatomy, primarily in the prefrontal cortex, which may affect psychological development following the emergence of robust changes in sex hormones.

中枢性性早熟（Central precocious puberty, CPP）已被证实对心理社会发展具有显著影响。此类与青春期早期相关的激素及心理社会功能变化，被认为与特定脑发育过程存在关联。然而，青春期相关激素成熟重塑人脑结构并调节心理社会转变的生物学机制仍不明晰，尤其是在CPP早期阶段。
本研究旨在明确CPP病程中受激素早期成熟效应影响的脑区，及其与心理功能的关联。本研究纳入65名年龄介于4.3至8.0岁的女童，所有受试者均接受3T磁共振系统的结构成像检查、完成心理测试，并接受促性腺激素释放激素（gonadotropin-releasing hormone, GnRH）激发试验，以识别下丘脑-垂体-性腺轴（hypothalamic–pituitary–gonadal axis, HPG轴）激活的激素表现。根据GnRH激发试验结果，28名女童被确诊为CPP，其余37名则被归类为非中枢性性早熟（non-central precocious puberty, NCPP）。在校正年龄、体重及身高因素后，计算并比较两组受试者的皮层参数。提取两组间存在显著组间差异的脑区，并与血清激素水平及心理参数进行相关性分析。
研究结果显示，CPP组女童的皮层厚度主要在右侧额中回喙部表现为更薄。该形态学差异与激发后雌二醇（estradiol, E2）水平呈正相关。进一步分析发现，更高的E2水平与更高的多动评分显著相关。早期CPP女童的HPG轴过早激活，似乎会对脑解剖结构产生重塑作用，主要累及前额叶皮层，这可能在性激素出现显著变化后对心理发展产生影响。