Emerging Roles of Kisspeptin in Sexual and Emotional Brain Processing

Comninos, Alexander; Dhillo, Waljit S.

doi:10.1159/000481137

Cited by 37 publications

(20 citation statements)

References 62 publications

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“…Collectively, these studies in humans and several other species demonstrate that kisspeptin signalling effectively integrates sensory processing with limbic pathways involved in sexual arousal, positive mood, and anxiety (for a current review of kisspeptin in these areas, please see [ 46 ]). Together with its established role as a modulator of reproductive hormone secretion, these data suggest that kisspeptin plays a key part in the integration of reproduction, sex, and emotion (Fig.…”

Section: Kisspeptinmentioning

confidence: 99%

Intrinsic links among sex, emotion, and reproduction

Yang

Comninos

Dhillo

2018

Cell. Mol. Life Sci.

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Species survival is dependent on successful reproduction. This begins with a desire to mate, followed by selection of a partner, copulation and in monogamous mammals including humans, requires emotions and behaviours necessary to maintain partner bonds for the benefit of rearing young. Hormones are integral to all of these stages and not only mediate physiological and endocrine processes involved in reproduction, but also act as neuromodulators within limbic brain centres to facilitate the expression of innate emotions and behaviours required for reproduction. A significant body of work is unravelling the roles of several key hormones in the modulation of mood states and sexual behaviours; however, a full understanding of the integration of these intrinsic links among sexual and emotional brain circuits still eludes us. This review summarises the evidence to date and postulates future directions to identify potential psycho-neuroendocrine frameworks linking sexual and emotional brain processes with reproduction.

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Section: Kisspeptinmentioning

confidence: 99%

Intrinsic links among sex, emotion, and reproduction

Yang

Comninos

Dhillo

2018

Cell. Mol. Life Sci.

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“…Mammalian reproductive physiology encompasses crucial links between reproductive hormones, brain functions, and behavior, in order to produce and coordinate a complex collection of reproductive functions. The reproductive hormone kisspeptin (encoded by the KISS1 gene), has recently been identified as the master regulator of the reproductive axis, with emerging roles in sexual and emotional behavior ( 1 – 6 ). To this end, kisspeptin and its cognate receptor (encoded by the KISS1R gene) are expressed in key emotional structures of the limbic system in both rodents ( 7 – 11 ) and humans ( 12 – 14 ).…”

Section: Introductionmentioning

confidence: 99%

Modulations of human resting brain connectivity by kisspeptin enhance sexual and emotional functions

Comninos¹,

Demetriou²,

Wall³

et al. 2018

JCI Insight

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BACKGROUND. Resting brain connectivity is a crucial component of human behavior demonstrated by disruptions in psychosexual and emotional disorders. Kisspeptin, a recently identified critical reproductive hormone, can alter activity in certain brain structures but its effects on resting brain connectivity and networks in humans remain elusive.METHODS. We determined the effects of kisspeptin on resting brain connectivity (using functional neuroimaging) and behavior (using psychometric analyses) in healthy men, in a randomized double-blinded 2-way placebo-controlled study.RESULTS. Kisspeptin’s modulation of the default mode network (DMN) correlated with increased limbic activity in response to sexual stimuli (globus pallidus r = 0.500, P = 0.005; cingulate r = 0.475, P = 0.009). Furthermore, kisspeptin’s DMN modulation was greater in men with less reward drive (r = –0.489, P = 0.008) and predicted reduced sexual aversion (r = –0.499, P = 0.006), providing key functional significance. Kisspeptin also enhanced key mood connections including between the amygdala-cingulate, hippocampus-cingulate, and hippocampus–globus pallidus (all P < 0.05). Consistent with this, kisspeptin’s enhancement of hippocampus–globus pallidus connectivity predicted increased responses to negative stimuli in limbic structures (including the thalamus and cingulate [all P < 0.01]).CONCLUSION. Taken together, our data demonstrate a previously unknown role for kisspeptin in the modulation of functional brain connectivity and networks, integrating these with reproductive hormones and behaviors. Our findings that kisspeptin modulates resting brain connectivity to enhance sexual and emotional processing and decrease sexual aversion, provide foundation for kisspeptin-based therapies for associated disorders of body and mind.FUNDING. NIHR, MRC, and Wellcome Trust.

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“…The anatomy, molecular biology, functions, and regulatory mechanism of hypothalamic kisspeptin–KissR system have been extensively studied, and summarized in a number of review articles for mammalian species ( 5 , 21 – 23 ) and for non-mammalian species ( 10 , 24 – 29 ). However, the knowledge on non-hypothalamic kisspeptin–KissR system is still limited ( 14 , 30 – 33 ). The role of non-hypothalamic kisspeptin signaling is scarcely examined in non-mammalian vertebrates.…”

Section: Introductionmentioning

confidence: 99%

Biological Significance of Kisspeptin–Kiss 1 Receptor Signaling in the Habenula of Teleost Species

Ogawa

Parhar

2018

Front. Endocrinol.

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Kisspeptin is a neuropeptide, encoded by kisspeptin 1 (KISS1)/Kiss1 gene, which primarily acts as the regulator of reproductive functions via its receptor, kisspeptin receptor (KissR) in vertebrates. In the brain, Kiss1 gene is mainly expressed in the hypothalamic region, but KissR gene is widely distributed throughout the brain, suggesting that kisspeptin–KissR system may be involved in not only reproductive, but also non-reproductive functions. In non-mammalian vertebrates, there are two or more kisspeptin and KissR types. The zebrafish (Danio rerio) possess two kisspeptin (Kiss1 and Kiss2) and their respective receptors [Kiss1 receptor (KissR1) and KissR2]. In the brain of zebrafish, while Kiss2 is expressed in the preoptic-hypothalamic area, Kiss1 is predominantly expressed in the habenula, an evolutionarily conserved epithalamic structure. Similarly, KissR1 is expressed only in the habenula, while KissR2 is widely distributed in the brain, suggesting that the two kisspeptin systems play specific roles in the brain. The habenular Kiss1 is involved in the modulation of the raphe nuclei and serotonin-related behaviors such as fear response in the zebrafish. This review summarizes the roles of multiple kisspeptin–KissR systems in reproductive and non-reproductive functions and neuronal mechanism, and debates the biological and evolutional significance of habenular kisspeptin–KissR systems in teleost species.

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Emerging Roles of Kisspeptin in Sexual and Emotional Brain Processing

Cited by 37 publications

References 62 publications

Intrinsic links among sex, emotion, and reproduction

Intrinsic links among sex, emotion, and reproduction

Modulations of human resting brain connectivity by kisspeptin enhance sexual and emotional functions

Biological Significance of Kisspeptin–Kiss 1 Receptor Signaling in the Habenula of Teleost Species

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