MON-670 Pituitary Expression of Brain-Derived Neurotrophic Factor (BDNF) and Projection of Hypothalamic BDNF-expressing Neurons

Abstract Disclosure: E.C. Tsao: None. A.F. Zhao: None. J.C. Han: None. C.E. Kinney: None. Objectives: Brain-derived neurotrophic factor (BDNF) plays important roles in embryologic development of the central nervous system and postnatally functions within the leptin-proopiomelanocortin pathway for the regulation of energy homeostasis. The role of BDNF in the regulation of the hypothalamic-pituitary axis is less well understood. We therefore sought to determine which hypothalamic nuclei containing BDNF-expressing neurons project to the pituitary. Methods: Fluorescence microscopy was used to image sectioned pituitary from [A] mice that doubly expressed cre recombinase (Cre) in BDNF-expressing cells (Bdnf-2A-Cre/+) and a global cre-dependent tdTomato (Ai9/+), and [B] Bdnf-2A-Cre/+ mice that received an intracranial injection of virus that expressed a cre-dependent tdTomato into the paraventricular (PVH), ventromedial (VMH), or lateral (LH) hypothalamic nucleus. Results: The neurohypophysis was devoid of tdTomato-expressing cell bodies. Within the adenohypophysis, the melanocyte-stimulating hormone (MSH)-producing pars intermedia was more densely packed with tdTomato-expressing cells than was the pars distalis. In mice with viral expression in the PVH or VMH, we detected no appreciable axonal or terminal tdTomato signal in the pituitary. However, tdTomato-positive axons and terminals were found in mice with viral expression in LH. Conclusions: These data suggest that the pituitary is a source of BDNF synthesis and secretion, and that BDNF-expressing neurons in the LH project to the pituitary. Further studies are needed to determine if these BDNF-expressing neurons from the LH release BDNF from their terminals into the pituitary as an additional source of BDNF separate from the BDNF synthesized within the pituitary itself. Presentation: Monday, July 14, 2025