Effects of Kisspeptin on Hormone Secretion in Humans

Studies of the actions of kisspeptin in human subjects have examined the effects of different kisspeptin isoforms, doses, and routes of administration on LH secretion, a surrogate measure of GnRH release. These studies, in addition to detailing how these different variables affect LH secretion in response to kisspeptin, have produced new insights into kisspeptin physiology: (1) Brief exposure to kisspeptin results in sustained GnRH release lasting similar to 17 min in men. (2) Women in different phases of the menstrual cycle have differences in their response to kisspeptin, suggesting that endogenous kisspeptin secretion and GnRH neuronal responsiveness vary in response to the changing sex-steroid environment across the menstrual cycle. (3) Kisspeptin resets the GnRH pulse generator in men, but does not appear to do so in women. (4) Continuous exposure to kisspeptin results in desensitization to kisspeptin, and thus kisspeptin has the potential to either stimulate or suppress reproductive endocrine activity depending on the mode of administration. These findings pave the way for future studies using kisspeptin as a physiologic, diagnostic, and therapeutic tool in both healthy adults and in patients with reproductive disorders.