ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Front Endocrinol (Lausanne). 2018 Apr 6;9:148

Pubertal onset and subsequently reproduction result from the awakening of a complex neuroendocrine machinery leading to the acceleration of the gonadotropin-releasing hormone (GnRH) secretion by the hypothalamus. Several neuronal, glial or peripheral factors have been identified as playing a major role in the onset of puberty¹. This paper reviews data obtained in non-human primates illustrating the crucial role played by kisspeptin and neurokinin B (NKB) in this pubertal activation of GnRH secretion. Both kisspeptin and NKB signaling appear to contribute to the pubertal increase in GnRH release independently or in concert in females while there seems to have no interaction between kisspeptin and NKB in sexually immature females. The contribution of direct NKB signaling to GnRH release, however, may be secondary, as NKB signaling to GnRH release does not change across puberty, whereas NKB signaling to kisspeptin release greatly increases. Thus, in females, kisspeptin signaling appears to be the main force driving the pubertal GnRH release increases. The role of NKB in the pubertal increase in GnRH release, however, requires further experiments. In females, reciprocal signaling pathways between kisspeptin and NKB neurons could provide the necessary efficiency and flexibility for the stimulation of GnRH release, which ensures complex reproductive functions, such as cyclic ovulations and pregnancy.

Separately, Chan et al.² recently described the first report of kisspeptin administration to pediatric subjects. Adult cohorts show either uniform responsiveness to kisspeptin (healthy adults) or uniform lack of responsiveness (adults with idiopathic hypogonadotropic hypogonadism). The ability to use kisspeptin to probe GnRH neuronal function presents a potential solution to a frequently encountered clinical challenge: the child presenting with delayed puberty. Children with delayed/stalled puberty showed a wide range of responses, with some showing a robust response and others showing little to no response. Further follow-up will determine whether responses to kisspeptin predict future pubertal entry for children with delayed puberty. The kisspeptin stimulation test has the potential to be a physiologically based method for diagnosing idiopathic hypogonadotropic hypogonadism in childhood.

1. Lomniczi A, Wright H, Ojeda SR. Epigenetic regulation of female puberty. Front Neuroendocrinol. 2015 Jan;36:90-107.

2. Chan YM, Lippincott MF, Kusa TO, Seminara SB. Divergent responses to kisspeptin in children with delayed puberty. JCI Insight. 2018 Apr 19;3(8).