Abstract:
Gonadotropin-releasing hormone (GnRH) is the central regulator of gonadotropins,
which stimulate gonadal function. Hypothalamic neurons that produce kisspeptin
and neurokinin B stimulate GnRH release. Inactivating mutations in the genes encoding
the human kisspeptin receptor (KISS1R, formerly called GPR54), neurokinin
B (TAC3), and the neurokinin B receptor (TACR3) result in pubertal failure. However,
human kisspeptin loss-of-function mutations have not been described, and contradictory
findings have been reported in Kiss1-knockout mice. We describe an inactivating
mutation in KISS1 in a large consanguineous family that results in failure of
pubertal progression, indicating that functional kisspeptin is important for puberty
and reproduction in humans. (Funded by the Scientific and Technological Research
Council of Turkey [TÜBİTAK] and others.)
