A major breakthrough occurred in 2003 for reproductive neuroendocrinology with the description of hypogonadotropic hypogonadism in human and mice bearing mutation in either kisspeptin gene (kiss) or its receptor (kissr) (90–92) and the following multiple studies stating that kisspeptins were the most potent secretagogues of GnRH in all mammals [for reviews (93–95)]. The gene discussed is KISS1; the disease is hypogonadotropic hypogonadism.