Timing of puberty - Which factors trigger pulsatile GnRH release and the onset of puberty?
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Puberty is the process of physical and psychological development towards adulthood, ultimately marked by the ability to reproduce. This development requires activation at all levels of the hypothalamus-pituitary-gonadal axis (HPG-axis): the hypothalamus for pulsatile secretion of gonadotropin-releasing hormone (GnRH), the pituitary for the pulsatile release of gonadotrophic factors and the gonads for generating gametes and gonadal steroids in response to these pulses. Pulsatile GnRH release from the hypothalamus is the primary drive to the HPG-axis. It seems that this is the limiting factor for the initiation of puberty. This system has the full potential to function at birth, but is being held in check. Interestingly, several direct and indirect upstream signaling pathways regulate the GnRH-secreting neurons: such as kisspeptin, leptin and gonadal steroids. Changes in these upstream factors might explain the initiation of pulsatile GnRH secretion and pubertal development. However, despite extensive research, it remains a mystery as to what exactly triggers the sudden onset of puberty. Furthermore, a clear sex difference exists in the presentation of puberty, occurring 1-2 years earlier in girls. This suggests that underlying mechanisms controlling GnRH secretion are differentially regulated in both sexes. The current review aims to give a critical overview of recent findings on factors that contribute to the initiation of puberty. Mechanisms that could underlie the sex difference in onset of puberty will be highlighted. New lines of research and remaining questions in the field will be discussed.