Interestingly, genetic loss-of-function studies in mice had previously suggested a developmental role of SIRT1 in early stages of GnRH neuron maturation; mice with congenital Sirt1 deficiency display hypogonadotropic hypogonadism (HH) due to defective neuronal migration42,43. Here, GNRH1 is linked to hypogonadotropic hypogonadism.