| Summary: | The novel hormone kisspeptin has been identified to play a pivotal role in the regulation of the hypothalamo-pituitary-gonadal axis. Previous studies from our laboratory have demonstrated that a bolus administration of kisspeptin-54 can acutely stimulate gonadotrophin release in healthy men and women. However, no previous studies have examined the effects of kisspeptin-54 to women with infertility. In this study I have examined the effects of acute and chronic administration of kisspeptin-54 on women with infertility due to hypothalamic amenorrhoea. This study has identified that acute administration of kisspeptin to women with hypothalamic amenorrhoea results in stimulation of reproductive hormones, but chronic administration for two weeks of twice daily injections of kisspeptin-54 at a dose of 6.4 nmol/kg, results in tachyphylaxis. I have conducted further studies to examine the time course of desensitisation of the kisspeptin receptor. I have also determined that a dosing regime of twice weekly administration of kisspeptin-54 results in sustained stimulation of gonadotrophin release. I have performed the first study of kisspeptin-10 administration to men and women. These results demonstrate that kisspeptin-10 stimulates gonadotrophin release in men as well as women during the preovulatory phase of the menstrual cycle; but fails to stimulate gonadotrophin release in women during the follicular phase. This reveals a sexual dimorphism in response to the kisspeptin-10. These findings have important ramifications for the potential use of kisspeptin-54 and kisspeptin-10 as a therapeutic agent in disorders of reproduction.
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