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

Abstract

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.

Relationship between Body Mass Index and Bone Turnover Markers in Girls with Idiopathic Central Precocious Puberty

“…Idiopathic central precocious puberty (ICPP) is the most common form of precocious puberty in girls, and it often leads to adverse efects on physical and psychological maturity [8]. Precocious puberty is a complex biological process of sexual development in which bones are observed to mature prematurely and rapidly.…”

Brain structure alterations in girls with central precocious puberty

“…The volume of the right precuneus and global cortical thickness showed age-dependent downward trends in both groups, suggesting the increased thickness of the right precuneus in the CPP group was not simply due to the acceleration of global brain development resulting from early sexual hormone increases. A previous observation study reported that the thinner right rostral middle frontal cortex in the CPP group as compared with that in the NC was a distinct feature of CPP ( Yang et al, 2019 ).…”

The impact of suppressing puberty on neuropsychological function: A review

“…22 In summary, puberty is characterised by both regressive and progressive stages of brain development. Unlike earlier developmental milestones, many of these processes are associated with pubertal stage rather than chronological age 22,[25][26][27] and hormonal regulation plays an important part in these developments. The prefrontal cortex undergoes significant rewiring during puberty, with corresponding behavioural changes in associated executive functions including impulse control, decision-making and goal-directed behaviours.…”