Purpose of reviewThe mechanism of puberty initiation remains an enigma,
despite extensive research in the field. Pulsatile pituitary
gonadotropin secretion under the guidance of hypothalamic
gonadotropin-releasing hormone (GnRH) constitutes a sine qua non for
pubertal onset. In turn, the secretion of GnRH in the human hypothalamus
is regulated by kisspeptin and its receptor as well as by permissive or
opposing signals mediated by neurokinin B and dynorphin acting on their
respective receptors. These three supra-GnRH regulators compose the
Kisspeptin, Neurokinin B and Dynorhin neurons (KNDy) system, a key
player in pubertal onset and progression.Recent findingsThe recent
discovery that makorin ring finger protein 3 is also involved in puberty
initiation provided further insights into the regulation of the KNDy
pathway. In fact, the inhibitory (-amino butyric acid, neuropeptide Y,
and RFamide-related peptide-3) and stimulatory signals (glutamate)
acting upstream of KNDy called into question the role of makorin ring
finger protein 3 as the gatekeeper of puberty. Meanwhile, the findings
that neuroestradiol' produced locally and endocrine disruptors from the
environment may influence GnRH secretion is intriguing. Finally,
epigenetic mechanisms have been implicated in pubertal onset through
recently discovered mechanisms.SummaryThe exact molecular machinery
underlying puberty initiation in humans is under intensive
investigation. In this review, we summarize research evidence in the
field, while emphasizing the areas of uncertainty and underlining the
impact of current information on the evolving theory regarding this
fascinating phenomenon