A Kiss and a PRomise

The discovery eleven years ago that deleterious mutations in the gene encoding the kisspeptin receptor (KISS1R) cause a failure of normal pubertal development in humans (1, 2) has propelled an entire field of neuroendocrine research focused on understanding how the ligand for this receptor, kisspeptin, regulates the hypothalamic-pituitary-gonadal axis. Hypothalamic kisspeptin potently stimulates GnRH secretion and the subsequent release of LH and FSH from the pituitary (3,–10). Kisspeptin neurons act as essential relay points to the GnRH neurons, integrating feedback from steroid hormones (7, 11, 12), circadian inputs (13,–17), and metabolic signals (18,–23).