SFEBES2016 Oral Communications Neuroendocrinology and Reproduction (6 abstracts)
Kisspeptin: A Novel Neuroendocrine Modulator of Sexual and Emotional Processing in Men
Alexander Comninos 1 , Matthew Wall 2 , Lysia Demetriou 2 , Amar Shah 1 , Sophie Clarke 1 , Shakunthala Narayanaswamy 1 , Alexander Nesbitt 1 , Chioma Izzi-Engbeaya 1 , Julia Prague 1 , Ali Abbara 1 , Risheka Ratnasabapathy 1 , Victoria Salem 1 , Gurjinder Nijher 1 , Channa Jayasena 1 , Mark Tanner 2 , Paul Bassett 3 , Amrish Mehta 4 , Eugenii Rabiner 2 , Christoph Honigsperger 5 & Waljit Dhillo 1
1Imperial College, London, UK; 2Imanova Centre for Imaging Sciences, London, UK; 3Statsconsultancy Ltd, Bucks, UK; 4Imperial College Healthcare NHS Trust, London, UK; 5University of Oslo, Oslo, Norway; 6University of Sao Paulo, Sao Paulo, Brazil.
Kisspeptin is a crucial activator of reproductive function, playing a critical role in the hypothalamus to activate GnRH neurons and downstream reproductive hormones. However, kisspeptin and its receptor are also expressed in other brain areas, yet little is known about their function here. The limbic system plays a key role in sexual and emotional behaviours and has a high expression of kisspeptin receptors. We therefore hypothesised that kisspeptin administration may modulate limbic brain activity in humans.
We mapped brain activity using fMRI in 29 heterosexual men (age 25.0±0.9 y) using a randomised blinded two-way placebo-controlled protocol. We used validated sexual/couple-bonding/negative/neutral themed images to stimulate limbic brain activity and determined if kisspeptin administration altered this response. Reproductive hormone measurements and psychometric assessments were performed throughout.
Kisspeptin administration increased circulating kisspeptin (P<0.001) and LH (P<0.001) but not testosterone (P=0.23) for the duration of the scans, as expected. Region of Interest analysis of the fMRI data revealed that kisspeptin (vs. vehicle) significantly enhanced activation in key limbic and para-limbic structures on viewing sexual images including the amygdala and cingulate. Viewing non-sexual couple-bonding images resulted in increased activity in similar structures with the addition of the thalamus and globus pallidus, important reward regions. Kisspeptin did not affect limbic brain activity on viewing negative images, but did enhance activity in the medial frontal gyrus. Consistent with this, psychometric analysis demonstrated that kisspeptin reduced negative mood (P=0.031).
Collectively, these data provide the first evidence that kisspeptin modulates limbic brain activity in response to sexual and emotional stimuli, and influences mood in healthy men. This is the first report of a novel role for kisspeptin in the integration of sexual and emotional processing in humans. Therefore, these data have important implications for our understanding of reproductive biology, as well as the development of kisspeptin as a potential therapeutic.
Volume 44
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Endocrine Abstracts
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