Abstract
BACKGROUND Successful reproduction is fundamental to all organisms, and in higher species relies on the integration of sensory cues of attraction with corresponding emotions and behaviours. However, these processes remain poorly understood. Kisspeptin is a potent activator of the reproductive axis with emerging evidence that it plays a role at the interface between reproduction and brain pathways controlling emotion and behavior. Indeed, kisspeptin receptors have also been identified in brain regions related to olfaction, sex and emotion. However, the effects of kisspeptin on human attraction have not been studied. To address this, we hypothesized that kisspeptin modulates olfactory and visual cues of attraction in healthy men. METHODS To test our hypothesis, we examined the effects of kisspeptin compared to vehicle administration on brain activity during olfactory and facial attractiveness tasks using functional MRI in 33 healthy heterosexual men (age 24.5±0.7y, BMI 22.9±0.8kg/m(2)). During the olfactory task, participants received a pleasant feminine scent (Chanel No.5) and during the facial attractiveness task they viewed images of unfamiliar female faces from a validated database. Participants also completed psychometric and behavioural questionnaires. RESULTS When exposed to a pleasant feminine scent, kisspeptin significantly enhanced brain activity compared to vehicle in regions related to olfaction and emotion. These included key components of the main olfactory network (p=0.008), along with other limbic structures which also express kisspeptin receptors such as the amygdala, hippocampus, thalamus, putamen, globus pallidus, and caudate (all p<0.05). When viewing female faces, kisspeptin significantly enhanced brain activity compared to vehicle in the primary aesthetic brain region; the medial prefrontal cortex (mPFC). This effect of kisspeptin on the mPFC was seen in response to faces rated high (p=0.0043), medium (p=0.0004) and low attractiveness (p=0.0085). Additionally, we observed correlations between the effects of kisspeptin on aforementioned brain activity and psychometric parameters of reward, orgasmic function and sexual desire (all p<0.01). CONCLUSIONS Collectively, we demonstrate for the first time that kisspeptin administration enhances brain responses to olfactory and visual cues of attraction in humans. Furthermore, this correlates with related psychometric parameters, thus providing key functional relevance. Our results point to a novel physiological pathway integrating attraction with reproductive hormones and behaviour in humans. These data have important implications for our understanding of human reproductive physiology, as well as the ongoing development of kisspeptin-based therapeutics to treat related reproductive disorders of body and mind.