Vasopressin (VP) is a peptide hormone secreted into the circulation from axon terminals in the neurohypophysis and also from soma and dendrites of magnocellular neuroendocrine cells (MNCs) within the supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus. While peripherally released VP promotes water conservation and blood pressure homeostasis, intranuclear release serves as an important autoregulatory mechanism influencing systemic peptide release. Polybrominated diphenyl ethers (PBDEs) are additive flame-retardants found in household furnishings. Levels of PBDEs are currently increasing in North Americans and PBDEs share a similar chemical structure with polychlorinated biphenyls (PCBs), which are known neurotoxicants.

My dissertation research focuses on the effects of PCBs and PBDEs on central vasopressin (VP) release as a model of endocrine disruption. The studies described herein further examine possible mechanisms of PCB/PBDE neurotoxicity by four different parameters: (1) We studied potential endocrine disruption effects utilizing both in vivo and in vitro exposure studies to determine if osmotically-stimulated VP release from SON tissue punches was altered. (2) We tested the potential of these toxicants to disrupt calcium signaling by exposing mitochondria) and microsomal preparations to environmentally relevant PBDE congeners and subsequently measured the effect on ⁴⁵Ca²⁺-uptake. (3) We determined whether circulating thyroid hormone levels were suppressed as a result of perinatal exposure of rat pups to PBDEs and subsequent measurement of circulating plasma thyroxine (T₄) and triiodothyronine (T₃). (4) We tested the potential of PCBs to disrupt nitric oxide signaling within the SON. We did this by employing NADPH-diaphorase histochemistry, which is a correlate of nitric oxide synthase activity in paraformaldehyde-fixed brain tissue. This dissertation extends the current knowledge of the mechanisms underlying PCB/PBDE neurotoxicity by showing that: (1) osmotically stimulated VP release within SON punches can be inhibited by both in vivo and in vitro exposure to PCBs or PBDEs. (2) Calcium buffering mechanisms are significantly compromised in both mitochondria and microsomal preparations exposed to PBDE in a cell-free preparation. (3) Circulating levels of thyroxine (T₄) are significantly reduced in rat pups perinatally exposed to PBDEs and (4) nitric oxide signaling is disrupted in both young and aged rats perinatally exposed to PCBs.