Macrophages Regulate Pituitary Hormone Regulation, Independent of Hypothalamic Signal 4793

Abstract Description Chronic inflammation disrupts the hormonal balance of the Hypothalamic-Pituitary-Gonadal axis, leading to reproductive disorders. Our research identifies macrophages as the main pituitary immune cells with unique transcriptional profiles of activation, phagocytosis, and hormone synthesis compared to other tissue-resident macrophages. We aim to explore the tissue-specific role of pituitary macrophages in hormone regulation. Notably, these macrophages exhibit high growth hormone (Gh) and prolactin (Prl) transcription levels. In vitro depletion of macrophages from mouse pituitaries resulted in decreased secretion of hormones and cytokines IFN-? and CXCL5. Reproductive hormone-producing mouse cell lines responded to IFN-? and CXCL5 in a dose- and time-dependent manner, independent of gonadotropin-releasing hormone from the hypothalamus, indicating a direct inflammatory impact on the pituitary. To further explore macrophage effects on hormone secretion, we are testing an in vivo pituitary macrophage depletion model using an adeno-associated virus (AAV) with cre- and Gh promoter-dependent caspase. Initial results suggest that macrophage depletion three weeks post-AAV injection is associated with increased follicle-stimulating hormone and decreased luteinizing hormone levels. 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. Funding Sources UCI Immunology T32 UCI MSTP T32 Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)