Puberty, A Sensitive Window of Hypothalamic Development and Plasticity

Puberty is a developmental period characterized by a broad range of physiologic changes necessary for the acquisition of adult sexual and reproductive maturity. These changes mirror complex modifications within the central nervous system, including within the hypothalamus. These modifications result in the maturation of a fully active hypothalamic-pituitary-gonadal (HPG) axis, the neuroendocrine cascade ensuring gonadal activation, sex steroid secretion, and gametogenesis. A complex and finely regulated neural network overseeing the HPG axis, particularly the pubertal reactivation of gonadotropin-releasing hormone (GnRH) secretion, has been progressively unveiled in the last 3 decades. This network includes kisspeptin, neurokinin B, GABAergic, and glutamatergic neurons as well as glial cells. In addition to substantial modifications in the expression of key targets, several changes in neuronal morphology, neural connections, and synapse organization occur to establish mature and coordinated neurohormonal secretion, leading to puberty initiation. The aim of this review is to outline the current knowledge of the major changes that neurons secreting GnRH and their neuronal and glial partners undergo before and after puberty. Emerging mediators upstream of GnRH, uncovered in recent years, are also addressed herein. In addition, the effects of sex steroids, particularly estradiol, on changes in hypothalamic neurodevelopment and plasticity are discussed.