Neuroendocrine plasticity and crosstalk in pubertal development

Puberty is a critical developmental stage during which individuals acquire the capacity for sexual reproduction. This transition involves a series of complex biological events primarily orchestrated by the activation of the hypothalamo-pituitary-gonadal (HPG) axis. Central to this process are gonadotropin-releasing hormone (GnRH) neurons, which play a key role in regulating reproductive maturation and function throughout life. However, the precise mechanisms that trigger the pubertal increase in GnRH activity remain incompletely understood. Evidence from our laboratory indicates that a profound remodeling of the hypothalamus is crucial for sexual maturation. In this review, we discuss findings from our research utilizing a combination of RNA sequencing, conditional genetic manipulation with mouse models and viral vectors, and systems neuroscience approaches. Our results reveal that the pubertal transition involves changes in the chemical phenotype and site-specific innervation of key hypothalamic neurons. Among these neuronal populations, those expressing growth hormone-releasing hormone (GHRH), kisspeptin, or dopamine transporter (DAT) are the focus of this review. Building upon data from other laboratories, our findings offer new insights into the neural and molecular mechanisms by which the hypothalamus orchestrates sexual maturation.