Investigating how the novel hormone kisspeptin modulates sexual and emotional brain processing in response to odour cues.

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Psychosexual dysfunction is caused by problems with sexual functioning due to a psychological rather than a physical problem. It involves several disorders (including impotence and reduced sexual desire) that collectively affect 1 in 3 people. There are severe consequences for individuals and their partners, impairing quality of life and interpersonal relationships as well as reducing chances for successful conception. In the UK the cost of treating psychosexual disorders with medical and psychological therapy is estimated at £32 million/year. Current medical treatments are limited by side-effects such as increased heart disease and cancer risk, and engagement with psychological therapies continues to be poor. Therefore, there is an unmet need to understand human sexual brain processing to help develop safer and more effective treatments. The limbic system is an area of the brain known to control emotions and instincts, including those related to sexual desire and reproductive behaviours. The limbic system interacts with several other brain centres including those involved in reproduction and interestingly, it also connects with brain areas that process smells. Smell underpins many important mating behaviours through the action of pheromones. Pheromones are chemicals that are released into the air and cause specific behaviours when smelled by an individual. There is growing evidence that pheromones affect human behaviour, for example men who smell t-shirts worn by women in their fertile phase, find that smell more sexually appealing compared to the smell of t-shirts from women who are not in their fertile phase. Kisspeptin is a hormone that reduces sexual aversion and negative mood when given to healthy men with specific brain changes seen on functional magnetic resonance imaging (fMRI). Recent work shows nerve fibres that contain kisspeptin make connections between the olfactory bulb (brain area processing smell), the limbic system and hypothalamus (a gland producing reproductive hormones). In animals, kisspeptin is closely linked with smell and mating e.g. when male mice lose their kisspeptin receptors, they also lose the ability to preferentially sniff out a female partner. Also, when female rats smell a male rat, they show increased kisspeptin activity in their brains. At present this relationship between kisspeptin, smell and sexual behaviour has not been explored in humans.I have designed an fMRI experiment using fragrance and pheromone smells to determine how kisspeptin affects brain response when these smells are presented to healthy men. Working alongside experts in this field, I have already collected pilot data which shows that smelling sexually arousing female fragrance activates limbic brain areas in healthy men. My preliminary work is very promising and demonstrates the imaging techniques I propose to use can detect activation in the brain areas of interest when smelling a female fragrance. To understand how kisspeptin in the bloodstream is able to carry out its actions on these brain areas, it is important to establish how kisspeptin gets across the blood-brain barrier into the brain. To do this, my laboratory has generated pilot data in a small group of mice showing that kisspeptin in the bloodstream builds up in the brain over time, which suggests that kisspeptin does cross the blood-brain barrier. I will now use specialised techniques to identify how kisspeptin moves across the blood-brain barrier. This will be beneficial for the development of kisspeptin-related treatments that can reach the brain in different ways. The overall aim is to use my results to help develop safer and more effective therapies for psychosexual disorders.