Kisspeptin and neurokinin B are both critical gatekeepers for reproductive maturation but there is still much to learn about how these neuropeptides stimulate GnRH secretion. This grant will anchor a collaboration between two investigators uniquely positioned to study the physiology of these peptides in non-human primates and humans in vivo. In the male monkey, the contributions of kisspeptin and NKB to GnRH secretion will be explored across puberty using novel assays and receptor agonists and antagonists. In the adult human male, exogenous kisspeptin administration to patients with idiopathic hypogonadotropic hypogonadism (IHH) will be assessed as a predictive tool for spontaneous recovery of GnRH pulsatile secretion. In the adolescent human male, exogenous kisspeptin will be explored as a diagnostic tool to distinguish between constitutional delay of puberty (CDP) and IHH. By focusing on the pubertal transition, and incorporating normal and pathophysiologic states, this grant will develop insights into reproductive maturation and develop diagnostic tools for pubertal disorders.