In order to contribute to an understanding of the hierarchy of roles of kisspeptin and NKB in the neuroendocrine control of GnRH pulsatility, we have administered kisspeptin to patients with hypogonadotropic hypogonadism resulting from naturally occurring loss-of-function mutations in the NKB ligand and its receptor. This evidence concerns the gene KISS1 and hypogonadotropic hypogonadism.