Moreover, an indispensable role of kisspeptin as a neuropeptide in the central nervous system regulating reproduction in humans, was uncovered by two studies published in 2003 (51, 52): Two groups from the US and France independently demonstrated inactivating mutations of the GPR54 gene in patients suffering from hypogonadotropic hypogonadism with pubertal failure. This evidence concerns the gene KISS1 and hypogonadotropic hypogonadism.