Researchers from Nagoya University’s Graduate School of Bioagricultural Sciences and the National Institute of Physiological Sciences in Japan delves into the intricate role of specific brain neurons in modulating hormones vital for ovarian functions such as follicular development and ovulation in females. Published in Scientific Reports, this research holds promise for advancing our comprehension and therapeutic approaches towards reproductive disorders in both animals and humans.
Central to this investigation are the kisspeptin neurons in the brain, orchestrating the release of hypothalamic gonadotropin-releasing hormone (GnRH) and pituitary follicle-stimulating hormone/luteinizing hormone (LH). These hormones play a pivotal role in reproductive processes across mammals, encompassing humans, by stimulating crucial ovarian functions like follicular development and ovulation.
The study delineates two key brain regions pivotal to this regulatory mechanism: the arcuate nucleus (ARC) and the anteroventral periventricular nucleus (AVPV). Within the ARC, kisspeptin neurons facilitate rhythmic secretion of GnRH/LH, sustaining regular follicular development and sex steroid production. Conversely, within the AVPV, these neurons instigate a surge of GnRH/LH, culminating in ovulation.
Mayuko Nagae, a postdoctoral fellow, and Yoshihisa Uenoyama, an associate professor at Nagoya University, shed light on their insights, stating, “Our observations underscore that kisspeptin neurons in the ARC exhibit both dynorphin and its receptor, whereas those in the AVPV solely express the receptor. This distinct expression pattern hints at a specialized role of these neurons in the fertilization process.” Nonetheless, the precise interplay between dynorphin and its receptor in modulating kisspeptin neurons remained elusive.
To unravel this intricate relationship, the team employed genetic modifications in female rats, targeting the deletion of the Kiss1 gene responsible for kisspeptin production exclusively in neurons expressing the dynorphin receptor. Intriguingly, rats exhibiting this genetic alteration manifested diminished kisspeptin neurons, experiencing prolonged estrous cycles, reduced ovarian weight, and diminished offspring compared to their counterparts.
Professor Hiroko Tsukamura, leading the research group at Nagoya University, expressed enthusiasm about these groundbreaking findings, emphasizing their implications. “Our study unveils the indispensable role of kisspeptin neurons, influenced by dynorphin, in orchestrating the GnRH/LH pulse and surge in female rats,” Professor Tsukamura remarked. She further accentuated the potential avenues this research opens, anticipating future endeavors to decipher the molecular intricacies governing kisspeptin neuronal dynamics. Ultimately, these insights hold transformative potential, paving the way for innovative therapeutic strategies addressing ovarian disorders in livestock and infertility challenges in humans.
Source: Nagoya University