Oral Presentation The International Congress of Neuroendocrinology 2014

Clinical use of Kisspeptin (#10)

Waljit Dhillo 1
  1. Imperial College, London, United Kingdom

Kisspeptin is a peptide which is encoded by the KiSS-1 gene and activates the G protein-coupled receptor GPR54. This system is a key regulator of mammalian and human reproduction. Animal studies have shown that GPR54-deficient mice have abnormal sexual development. Central and peripheral administration of kisspeptin stimulates the hypothalamic-pituitary-gonadal (HPG) axis. In humans, inactivating GPR54 or KiSS-1 gene mutations cause normosmic hypogonadotrophic hypogonadism whilst activation of GPR54 signalling is associated with premature puberty.

In healthy human volunteers, the acute intravenous administration of kisspeptin potently increases plasma LH levels and significantly increases plasma FSH and testosterone without side effects in both males and in females. In female volunteers kisspeptin stimulates gonadotropin release most potently in the preovulatory phase of the menstrual cycle. Kisspeptin stimulates reproductive hormone release through the release of endogenous GnRH. Therefore, administration of kisspeptin to stimulate reproductive hormone release could represent a more natural way to stimulate hormone release in infertility e.g. recent studies suggest that kisspeptin might have therapeutic benefit as a more physiological trigger of oocyte maturation during IVF treatment than hCG which is currently used.

The kisspeptin system has also been shown to be important in the generation of GnRH pulses which are vital for normal fertility. Recent data shows that in healthy male volunteers acute administration of kisspeptin may be able to reset the hypothalamic GnRH clock and that an infusion of kisspeptin can stimulate pulsatile LH release. Infusion of kisspeptin has also been shown to stimulate pulsatile LH release in normal women, patients with inactivating mutations in NKB or its receptor, patients with biochemical hypogonadism due to diabetes and in women with hypothalamic amenorrhea. The ability of kisspeptin administration to stimulate pulsatile LH release further highlights its importance as a potential novel therapeutic target for the treatment of infertility.