A groundbreaking study led by the University of Cordoba and IMIBIC has uncovered the first direct interaction between kisspeptins—key proteins involved in sexual development—and astrocytes, which are non-neuronal cells in the nervous system. This discovery paves the way for a deeper understanding of how the reproductive system is regulated.
Sexual reproduction relies on an intricate network of regulatory systems that work together in harmony. Among these, kisspeptins are essential molecules produced mainly in the hypothalamus, playing a vital role in reproductive system regulation. The new research coordinated by the University of Cordoba and IMIBIC details a novel molecular pathway that contributes to reproductive control, specifically involving these proteins.
The study’s findings, spearheaded by researcher Encarnación Torres, reveal that kisspeptins influence the behavior of astrocytes, which are important non-neuronal cells in the central nervous system. Previously, it was thought that kisspeptins only interacted with neurons. This newly published study is the first to demonstrate that these proteins also affect other types of brain cells.
A parallel pathway for “self-regulation”
Conducted primarily on preclinical models with mice and in collaboration with various institutions, including the Spanish Biomedical Research Centre in the Physiopathology of Obesity and Nutrition (CIBEROBN) and universities in Cambridge (UK) and Lille (France), the study also highlights a potential new role for this molecular pathway. As noted by co-director Manuel Tena-Sempere alongside researcher Antonio Romero, the results imply that this interaction serves as a parallel route essential for the self-regulation of the brain’s reproductive circuits.
For decades, it has been understood that kisspeptins activate specific brain neurons known as GnRH, which are crucial for regulating the reproductive axis. This new study adds that kisspeptins also engage with astrocytes to prevent excessive activation of these neurons, thereby avoiding overstimulation that could disrupt reproductive function. Essentially, this serves as a control mechanism to maintain balance. “In physiological circuits, more is not necessarily better, as overexpression can lead to the opposite effect,” emphasizes Tena.
The role of diet
The Tena-Sempere research team has been investigating the hypothalamus to gain a clearer perspective on how this brain region regulates both obesity and puberty and how these two factors are interconnected.
The study’s findings have also indicated that specific reproductive issues linked to obesity are influenced by kisspeptins’ actions on astrocytes, as observed in changes in reproductive responses in rodents fed high-fat diets.
This work marks progress in the understanding of the intricate regulation of the reproductive system. Although it is primarily foundational research, its aim is to enhance the understanding of the interaction between metabolic and reproductive states, ultimately leading to improved diagnostic methods, the exploration of new therapeutic targets, and the development of treatment options.
