The master regulator of the reproductive hormone axis — controls GnRH pulsatility, LH, and downstream sex hormones.
Kisspeptin (encoded by the KISS1 gene) is the endogenous ligand for the GPR54 receptor on GnRH neurons. Kisspeptin neurons in the arcuate nucleus (KNDy neurons) drive pulsatile GnRH release, which in turn produces LH and FSH pulses from the pituitary — the foundational driver of gonadal hormone production and reproductive function.
Kisspeptin deficiency or GPR54 mutations cause hypogonadotropic hypogonadism with infertility. Kisspeptin agonists are under clinical investigation for stimulating ovulation in IVF, treating hypogonadism, and as a diagnostic test of the HPG axis.
Kisspeptin-54 (the longest form) has shown efficacy in stimulating LH and testosterone in men with functional hypogonadotropic hypogonadism in clinical trials, with a favourable safety profile compared to exogenous hCG.