MICA: Investigating kisspeptin receptor signalling to improve the treatment of reproductive disease

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Kisspeptin is the central controller of reproductive hormone secretion from the hypothalamus. Our group's research has identified a number of reproductive disorders that would benefit from treatment using kisspeptin based therapies. However, there remain many unanswered questions as to how kisspeptin interacts with its receptor. For example, it is known that giving too much kisspeptin can reduce the ability of kisspeptin to induce hormonal stimulation. Additionally, levels of oestrogen at the time of administration can affect the hormonal response to kisspeptin. Moreover, a number of new drugs have been generated that act through the kisspeptin receptor. However, the precise way by which these new kisspeptin based drugs or how oestrogen interacts with the kisspeptin receptor has not been fully described.Therefore, we will conduct research to understand how natural kisspeptins and newly developed drugs that act on the kisspeptin receptor exert their effects inside cells, how this is altered in times of excessive stimulation, and the effect of changes in oestrogen levels on these processes. In this proposal, we have assembled a team of experts from across the globe to conduct cutting edge experiments to better understand signalling at the kisspeptin receptor. We will work with an industry partner to test an oral kisspeptin based drug that is still in development, as well as other recently developed kisspeptin receptor stimulators. We will use an animal model of hypothalamic amenorrhoea (one of the commonest causes of loss of periods and subfertility) to develop a protocol using a kisspeptin-based therapy that can be used to restore reproductive health. In summary, it is essential to better understand the action of kisspeptin and kisspeptin-based drugs at the kisspeptin receptor. This work will enable us to develop treatment protocols using kisspeptin or kisspeptin-like drugs that will improve the care of patients suffering from reproductive disorders.