A study led by the University of Cordoba and IMIBIC provides the first evidence of a direct interaction between kisspeptins, proteins crucial for sexual development, and astrocytes, non-neuronal cells of the nervous system, paving new avenues for understanding the regulation of the reproductive system.
Sexual reproduction is protected by a sophisticated network of regulatory systems that function in a coordinated manner. Within this framework, one of the most important molecules are kisspeptins, proteins produced mainly in the hypothalamus that play a crucial role in the regulation of the reproductive system. New research, coordinated by the University of Cordoba and IMIBIC, has succeeded for the first time in describing a new molecular pathway involved in the control of reproduction that involves precisely these proteins.
The results of the study, in which researcher Encarnación Torres is the first author, indicate that these molecules, called kisspeptins, modulate the activity of astrocytes, a type of non-neuronal cells that play key functions in the central nervous system. It was previously believed that all of these interactions of kisspeptins took place with neurons. This study provided the first evidence that these proteins also act on other cellular elements of the brain.
A parallel trajectory for ‘self-regulation’
The study, carried out mainly in preclinical models using mice, and in collaboration with other institutions such as the Spanish Biomedical Research Center in the Physiopathology of Obesity and Nutrition (CIBEROBN) and the Universities of Cambridge (England) and Lille (France), succeeded also to shed some light on the usefulness of this new molecular route. As Manuel Tena-Sempere, co-director of the work along with researcher Antonio Romero, points out, the results suggest that this interaction acts as a kind of parallel pathway that supports the self-regulation of the brain’s reproductive circuits.
It has been known for decades that kisspeptins stimulate a set of brain neurons known as GnRH, which control the reproductive axis. According to what has been discovered in this new research, kisspeptins also interact with astrocytes precisely to prevent the overactivation of these neurons in the brain, thus preventing excessive stimulation, which could cause malfunctions in the reproductive system. In short, it is a control mechanism that allows balance to be maintained. “As often happens with physiological circuits, more is not always better, and overexpression can produce the opposite of what is aimed for,” Tena points out.
The role of nutrition
Tena-Sempere’s team has spent years studying the hypothalamus to understand more deeply how this part of the brain controls obesity and puberty, and especially how these two factors are related.
In this regard, the results of the work have also shown how certain reproductive changes associated with obesity are also modulated by the action of kisspeptins on astrocytes, something that has been verified by analyzing changes in the reproductive responses of rodents subjected to high-fat diets.
The work thus represents a step forward in understanding the complex regulation of the reproductive system. And while it can be classified as fundamental to translational science, its aim is to better understand how metabolic and reproductive states interact to ultimately diagnose changes, explore new therapeutic targets, and develop pharmacological treatments.
