Kisspeptin modulates sexual and emotional brain processing in humans
Alexander N. Comninos, … , Stephen R. Bloom, Waljit S. Dhillo
Alexander N. Comninos, … , Stephen R. Bloom, Waljit S. Dhillo
Published February 1, 2017; First published January 23, 2017
Citation Information: J Clin Invest. 2017;127(2):709-719. https://doi.org/10.1172/JCI89519.
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Categories: Clinical Medicine Neuroscience Reproductive biology

Kisspeptin modulates sexual and emotional brain processing in humans

Abstract

BACKGROUND. Sex, emotion, and reproduction are fundamental and tightly entwined aspects of human behavior. At a population level in humans, both the desire for sexual stimulation and the desire to bond with a partner are important precursors to reproduction. However, the relationships between these processes are incompletely understood. The limbic brain system has key roles in sexual and emotional behaviors, and is a likely candidate system for the integration of behavior with the hormonal reproductive axis. We investigated the effects of kisspeptin, a recently identified key reproductive hormone, on limbic brain activity and behavior.

METHODS. Using a combination of functional neuroimaging and hormonal and psychometric analyses, we compared the effects of kisspeptin versus vehicle administration in 29 healthy heterosexual young men.

RESULTS. We demonstrated that kisspeptin administration enhanced limbic brain activity specifically in response to sexual and couple-bonding stimuli. Furthermore, kisspeptin’s enhancement of limbic brain structures correlated with psychometric measures of reward, drive, mood, and sexual aversion, providing functional significance. In addition, kisspeptin administration attenuated negative mood.

CONCLUSIONS. Collectively, our data provide evidence of an undescribed role for kisspeptin in integrating sexual and emotional brain processing with reproduction in humans. These results have important implications for our understanding of reproductive biology and are highly relevant to the current pharmacological development of kisspeptin as a potential therapeutic agent for patients with common disorders of reproductive function.

FUNDING. National Institute for Health Research (NIHR), Wellcome Trust (Ref 080268), and the Medical Research Council (MRC).

Authors

Alexander N. Comninos, Matthew B. Wall, Lysia Demetriou, Amar J. Shah, Sophie A. Clarke, Shakunthala Narayanaswamy, Alexander Nesbitt, Chioma Izzi-Engbeaya, Julia K. Prague, Ali Abbara, Risheka Ratnasabapathy, Victoria Salem, Gurjinder M. Nijher, Channa N. Jayasena, Mark Tanner, Paul Bassett, Amrish Mehta, Eugenii A. Rabiner, Christoph Hönigsperger, Meire Ribeiro Silva, Ole Kristian Brandtzaeg, Elsa Lundanes, Steven Ray Wilson, Rachel C. Brown, Sarah A. Thomas, Stephen R. Bloom, Waljit S. Dhillo

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Figure 2

Sexual images, effects of kisspeptin on brain activity, and correlations with reward and sexual aversion.

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Sexual images, effects of kisspeptin on brain activity, and correlations...
(A) Whole-brain analysis of enhanced activity by kisspeptin administration in response to sexual images. Am, amygdala; GP, globus pallidus; PCC, posterior cingulate cortex; P, putamen; T, thalamus. (B) Percentage of mean BOLD signal change in a priori limbic and paralimbic anatomically defined ROIs in response to sexual images. Data depict within-participant paired raw data, mean ± SEM. *P < 0.05, paired 2-sided t test. Ant., anterior, Post., posterior. (C) Correlation between baseline reward score (BAS reward score) and enhancement of hippocampal activity by kisspeptin in response to sexual images. (D) Correlation between change in sexual aversion (SADI-negative) and putamen enhancement by kisspeptin (KP) in response to sexual images. Partial correlation testing, adjusted for visit order. n = 29.