SAT-003 Macrophages Regulate Pituitary Hormone Secretion, Independent of Hypothalamic Input

Abstract Disclosure: Z. Del Mundo: None. J. Ha: None. A. Zhang: None. K.D. Wiggins: None. G. De Robles: None. D. Nicholas: None. Chronic inflammation disrupts hormonal balance in the Hypothalamic-Pituitary-Gonadal (HPG) axis, contributing to reproductive disorders. While immune cells in the hypothalamus and ovaries have been extensively studied, their impact on the pituitary remains largely unexplored. Our research identifies macrophages as the primary pituitary immune cells, exhibiting unique transcriptional profiles for immune activation, phagocytosis, and hormone synthesis compared to other tissue-resident macrophages. Notably, these macrophages demonstrate high growth hormone (Gh) and prolactin (Prl) transcription levels. To investigate the role of pituitary macrophages in hormone regulation, we depleted macrophages from mouse pituitaries both in vitro and in vivo. In vitro macrophage depletion decreased secretion of gonadotropins, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and cytokines, IFN-ɣ and CXCL5. LβT2 gonadotrope cells responded to IFN-ɣ and CXCL5 in a dose- and time-dependent manner, with or without gonadotropin-releasing hormone induction from the hypothalamus, which indicates a direct inflammatory impact on the pituitary. Furthermore, our in vivo macrophage depletion mouse model validates FSH and LH reduction upon pituitary macrophage depletion using adeno-associated virus (AAV) with Cre- and Gh promoter-dependent caspase. Interestingly, estrous cycle length and average time spent per cycle stage remained unchanged upon depletion. These findings highlight the essential role of pituitary macrophages in hormonal regulation and pave the way to potential immunotherapeutic strategies for restoring hormonal balance in reproductive disorders. Presentation: Saturday, July 12, 2025