Influence of the hypothalamus-pituitary-gonadal axis reactivation and corresponding surging sex hormones on the amplitude of low-frequency oscillations in early pubertal girls: A resting state fMRI study

Abstract

Background: There has been a myriad of neuroimaging studies that have suggested that pubertal stages and sex steroid fluctuations contribute to pubertal brain maturation. Investigations on the influence of hypothalamus-pituitary-gonadal (HPG) axis reactivation and the correlated elevated sex hormones on brain maturation have not unraveled these interactions to date. Here, we aimed to explore the impact of the reactivated HPG axis on spontaneous brain activity changes, by analyzing the amplitude of low-frequency fluctuation (ALFF) in developing girls aged 8-11 years old.

Methods: The gonadotropin-releasing hormone (GnRH) stimulation test was used to determine the HPG axis status and categorize subjects into two groups (HPG+ or HPG- group). Intelligence quotient (IQ) and the parent-rated Child Behavior Checklist (CBCL) were used to evaluate cognitive and behavioral performance. Two-sample t-tests were used to compare intergroup differences, the relations between brain areas' activities, age and hormonal levels were conducted by Pearson or Spearman correlation analyses.

Results: Compared with the HPG- group, the HPG+ group showed decreased ALFF values in the left superior temporal gyrus (STG) but increased ALFF values in the right superior frontal gyrus (SFG). In addition, in the HPG+ group, prolactin (PRL) levels were positively correlated with ALFF values in the right SFG, and there was significant negative correlation between ALFF values in the left STG and CBCL activities scores.

Limitations: Due to the cross-sectional design of the present study, further study is needed to determine the relationships between age, reawakening of the HPG axis and related sex hormones and spontaneous brain activity change.

Conclusions: These findings suggested that the reactivated HPG axis and elevated PRL level could affect changes in brain activity and this effect may be the neuroendocrine basis of mood, cognition, and social behavior changes in early pubertal girls.

Keywords: Amplitude of low-frequency fluctuation (ALFF); Hypothalamus–pituitary–gonadal (HPG) axis; Sex steroid hormones; Spontaneous brain activity.