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0This research article demonstrates that Rank signaling in hypothalamic microglia acts as a vital regulator of the hypothalamic-pituitary-gonadal (HPG) axis, which governs sexual development and fertility. Through various mouse models, the authors show that a lack of Rank leads to a significant decrease in gonadotropin-releasing hormone (GnRH), causing conditions like hypogonadotropic hypogonadism and impaired puberty. The study identifies that these microglia interact with GnRH neurons particularly within the median eminence, and their activity is essential for proper reproductive function in both sexes. Furthermore, the researchers discovered rare RANK gene variants in human patients suffering from similar reproductive disorders, reinforcing the clinical relevance of this pathway. Ultimately, the findings suggest that microglia activation via Rank is a fundamental requirement for maintaining the hormonal balance necessary for reproduction.
References:
Collado-Sole A, Borjini N, Zhai J, et al. Microglia Rank signaling regulates GnRH neuronal function and the hypothalamic-pituitary-gonadal axis[J]. Science, 2026: eaeb6999.
