This Peptide May Explain Female Sexual Behavior

In most animals, a female’s sex drive rises to coincide with ovulation, which increases her chances of mating and reproducing.

At the point of ovulation, females find particular males more attractive and adopt a position that makes them available for mating, which is known as lordosis behavior.

The behavior is well-described, and some of the main hormonal players are known. However, the neural circuits that underpin the coordination of ovulation, sexual motivation, and mate preference have remained elusive.

Because mice are nocturnal, their sense of smell is particularly important. As such, pheromones are known to play an important role in mating behavior. But how behavior and hormonal activity are sparked in unison is not yet understood.

The importance of kisspeptin

Using a mouse model to experiment, the team were particularly interested in a neuropeptide called kisspeptin, which is known to be involved in sexual maturation.

For example, during puberty, kisspeptin initiates the secretion of gonadotropin- releasing hormone (GnRH), a hormone important for triggering female sexual cycles.

As an aside, it’s worth explaining how this peptide got its intriguing name, and it has nothing to do with sex: kisspeptin DNA was first isolated in Dr. Danny Welch’s laboratory in Hershey, PA. He named it KISS1 because Hershey is the hometown of Hershey’s Kisses.

In the new study, the team demonstrated that pheromones secreted by male mice activate neurons in the “rostral periventricular area of the third ventricle (RP3V) of the hypothalamus.” RP3V neurons, which are found in much greater numbers in female mice, produce kisspeptin.

Once released, kisspeptin stimulates GnRH neurons. The team showed that in a strain of mutant mice that lack GnRH secretion, the females did not show male- directed preference. So, it seems that the activation of these particular neurons drives a female’s attraction to males.

At the same time, kisspeptin initiates a parallel signal that triggers the release of nitric oxide (NO), a neurotransmitter that has previously been linked with sexual behavior.

Mutant female mice that do not express NO synthase — an enzyme important in the production of NO — showed a significant reduction in lordosis behavior. In other words, they did not display normal sexual behavior.

Understanding sexual behavior

This is the first time that neurons in the RP3V have been identified as important in orchestrating female sexual behavior in mice. The findings also underline the importance of kisspeptin in coordinating sexual behavior.

“This work,” explains Prof. Boehm, “has provided new insight into how the brain decodes signals from the outside world and then translates these environmental cues into behavior.

“In many animals,” he continues, “sexual behavior is timed to occur with ovulation to ensure the highest possible chance of fertilization and, therefore, continuation of the species.”

“Until now, little was known about how the brain ties together ovulation, attraction, and sex. Now we know that a single molecule — kisspeptin — controls all of these aspects through different brain circuits running in parallel with one another.”

Prof. Ulrich Boehm

Interesting in their own right, these findings also open up new avenues of study. They might form the basis of innovative new treatments for psychosexual disorders, such as hyposexual desire disorder.

As Prof. Bakker explains, “There are currently no good treatments available for women suffering from low sexual desire. The discovery that kisspeptin controls both attraction and sexual desire opens up exciting new possibilities for the development of treatments for low sexual desire.”

Kisspeptin therefore seems to be vital for combining both attraction to the opposite sex and sexual behavior. Further studies will be needed to confirm the conclusions, but the role of kisspeptin in sexual activity is now cemented.

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