ToxSci Advance Access published online on April 13, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfm086
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Polybrominated Diphenyl Ethers (PBDEs) and Ortho-substituted Polychlorinated Biphenyls (PCBs) as Neuroendocrine Disruptors of Vasopressin Release: Effects during Physiological Activation in vitro and Structure-Activity Relationships
1 Environmental Toxicology Graduate Program, University of California, Riverside, 92521, USA 2 Cellular and Molecular Toxicology Branch, Neurotoxicology Division, NHEERL, ORD, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA 3 Department of Cell Biology and Neuroscience, University of California, Riverside, CA 92521, USA
Address all correspondence to: Prasada Rao S. Kodavanti, Ph.D., Cellular and Molecular Toxicology Branch, Neurotoxicology Division, B 105-06, NHEERL / ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA, Phone: 919-541-7584, Fax: 919-541-0717, E-mail: kodavanti.prasada{at}epa.gov
Received January 17, 2007; revision received March 23, 2007; accepted April 7, 2007
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Abstract |
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The neuropeptide, vasopressin (VP) is synthesized in magnocellular neuroendocrine cells (MNCs) located within the supraoptic (SON) and paraventricular (PVN) nuclei of the mammalian hypothalamus. VP has multiple functions including maintenance of body fluid homeostasis, cardiovascular function, learning and memory and nervous system development. Polybrominated diphenyl ethers (PBDEs), used as additive flame retardants, have been shown to interfere with hormone metabolism and function. Previously, we demonstrated that the technical polychlorinated biphenyl (PCB) mixture, Aroclor 1254, inhibits somatodendritic VP release from the SON of osmotically stimulated rats. The objectives of the current study were to test whether PBDEs affect central VP release in a similar manner and to determine the potency of several PCB and PBDE congeners in order to identify a common mode of action for these persistent chemicals. The current work shows that the commercial PBDE mixture (DE-71) significantly decreased somatodendritic VP release from rat SON punches in a strain-independent manner. In addition, the specific congeners PBDE 47 and PCB 47 (15 µM and 5 µM) were also neuroactive in this system. To explore structure/activity relationships, we compared the effects of PBDE 77 with PCB 77. PBDE 77, but not PCB 77 significantly reduced VP release. These results show that like PCBs, PBDEs perturb signaling mechanisms responsible for hormone release, and that environmentally relevant PBDE congeners are more neuroactive than the commercial mixtures with non-coplanarity of these compounds playing a role in promoting neuroactivity.
Key Words: polychlorinated biphenyls; polybrominated diphenyl ethers; neurotoxicity; supraoptic nucleus; neuroendocrine disruption; hypothalamus; intracellular signaling; organohalogen compounds; osmoregulation; structure-activity relationships.