Dataset Information

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).

SUBMITTER: Comninos AN

PROVIDER: S-EPMC5272173 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Publications

Kisspeptin modulates sexual and emotional brain processing in humans.

Comninos Alexander N AN Wall Matthew B MB Demetriou Lysia L Shah Amar J AJ Clarke Sophie A SA Narayanaswamy Shakunthala S Nesbitt Alexander A Izzi-Engbeaya Chioma C Prague Julia K JK Abbara Ali A Ratnasabapathy Risheka R Salem Victoria V Nijher Gurjinder M GM Jayasena Channa N CN Tanner Mark M Bassett Paul P Mehta Amrish A Rabiner Eugenii A EA Hönigsperger Christoph C Silva Meire Ribeiro MR Brandtzaeg Ole Kristian OK Lundanes Elsa E Wilson Steven Ray SR Brown Rachel C RC Thomas Sarah A SA Bloom Stephen R SR Dhillo Waljit S WS

The Journal of clinical investigation 20170123 2

<h4>Background</h4>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 hormona ...[more]

PMID: 28112678

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Project description:GPR54 is a G-protein-coupled receptor, which binds kisspeptins and is widely expressed throughout the brain. Kisspeptin-GPR54 signaling has been implicated in the regulation of pubertal and adulthood gonadotropin-releasing hormone (GnRH) secretion, and mutations or deletions of GPR54 cause hypogonadotropic hypogonadism in humans and mice. Other reproductive roles for kisspeptin-GPR54 signaling, including the regulation of developmental GnRH secretion or sexual behavior in adults, have not yet been explored. Using adult wild-type (WT) and GPR54 knock-out (KO) mice, we first tested whether kisspeptin-GPR54 signaling is necessary for male and female sexual behaviors. We found that hormone-replaced gonadectomized GPR54 KO males and females displayed appropriate gender-specific adult sexual behaviors. Next, we examined whether GPR54 signaling is required for proper display of olfactory-mediated partner preference behavior. Testosterone-treated WT males preferred stimulus females rather than males, whereas similarly treated WT females and GPR54 KO males showed no preference for either sex. Because olfactory preference is sexually dimorphic and organized during development by androgens, we assessed whether GPR54 signaling is essential for sexual differentiation of other sexually dimorphic traits. Interestingly, adult testosterone-treated GPR54 KO males displayed "female-like" numbers of tyrosine hydroxylase-immunoreactive and Kiss1 mRNA-containing neurons in the anteroventral periventricular nucleus and likewise possessed fewer motoneurons in the spino-bulbocavernosus nucleus than did WT males. Our findings indicate that kisspeptin-GPR54 signaling is not required for male or female copulatory behavior, provided there is appropriate adulthood hormone replacement. However, GPR54 is necessary for proper male-like development of several sexually dimorphic traits, likely by regulating GnRH-mediated androgen secretion during "critical windows" in perinatal development.

Dataset Information

Kisspeptin modulates sexual and emotional brain processing in humans.

Background

Methods

Results

Conclusions

Funding

Publications

Kisspeptin modulates sexual and emotional brain processing in humans.

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