# Neurotrophic Control of Puberty: From Molecular Signaling to Disorders of Pubertal Timing

## TL;DR

This review explores how neurotrophins regulate the timing of puberty and their role in related disorders, integrating findings from animal and human studies.

## Contribution

The paper offers a comprehensive synthesis of experimental and clinical evidence on neurotrophin signaling in pubertal timing.

## Key findings

- Neurotrophins like BDNF influence hypothalamic maturation and GnRH neuron activation.
- Disrupted neurotrophin signaling is linked to disorders such as precocious and delayed puberty.
- Human studies suggest a potential role for neurotrophins in pediatric endocrine diagnostics and therapies.

## Abstract

The onset of puberty is a critical developmental milestone regulated by complex neuroendocrine networks that integrate genetic, metabolic, and environmental cues. Among the molecular systems coordinating this transition, neurotrophins—including brain-derived neurotrophic factor (BDNF), nerve growth factor, neurotrophin-3, and neurotrophin-4/5—have emerged as important modulators of hypothalamic maturation and the activation of gonadotropin-releasing hormone (GnRH) neurons. Beyond their established roles in neuronal survival and differentiation, neurotrophins contribute to hypothalamic circuit plasticity, influence GnRH neuronal activity, and participate in the integration of metabolic and environmental signals relevant to reproductive maturation. Experimental studies, primarily based on animal and cellular models, demonstrate that BDNF and its receptor play a role in normal pubertal onset, whereas disruptions in neurotrophin signaling have been implicated in central precocious puberty, delayed puberty, and hypogonadotropic hypogonadism. In humans, available evidence is more limited and derives mainly from genetic studies, circulating neurotrophin measurements, and clinical observations. This review provides an integrative synthesis of current experimental and clinical data on neurotrophin-mediated regulation of pubertal timing, highlighting both physiological mechanisms and pathological conditions. While neurotrophins represent promising modulators at the intersection of neurodevelopment, metabolism, and reproduction, further longitudinal and translational human studies are required to define their diagnostic and therapeutic potential in pediatric endocrinology.