Endocrine Abstracts

Puberty is a major event in human development that impacts the individual, the family and society in general, but with exception of its endocrinology the fundamental biology underlying the process is poorly understood. Puberty is the result of the complete activation of the pituitary-gonadal axis that, in man, is triggered by re-augmentation of pulsatile hypothalamic GnRH release after approximately a decade of pre-pubertal development during which time this mode of neuropeptide secretion is held in check by a gonad-independent neurobiological brake. Fundamental understanding of the neuronal basis of GnRH pulse generation has advanced dramatically since the discovery in 2003 of the importance of hypothalamic kisspeptin signaling to the reproductive axis: indeed compelling evidence is beginning to emerge that indicates kisspeptin release (at the level of the GnRH nerve terminals in the median eminence) from neurons located in the arcuate/infundibular nucleus provides the output of the pulse generator. The mechanisms that restrain the GnRH pulse generator from infancy until puberty and therefore suppress the pulsatile kisspeptin drive to the GnRH neuronal network, and the physiological control system that times, first, the application during infancy and, then, removal of this restraint at the end of juvenile development remain a mystery. While insight is being provided by molecular genetics of human disorders (e.g. makorin ring finger protein full 3), animal models for pursuing such leads are limited. Species such as the mouse, which are genetically tractable, do not exhibit a puberty that is delayed by a robust “primate like” neurobiological brake. Although the monkey provides a more suitable model for the human situation, studies of non-human primates are costly and difficult to execute; a situation that is exacerbated by the strengthening socio-political climate that views animal research, and particularly that on primates, negatively.