ToxSci Advance Access originally published online on April 13, 2007
Toxicological Sciences 2007 98(1):178-186; doi:10.1093/toxsci/kfm086
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Polybrominated Diphenyl Ethers and ortho-Substituted Polychlorinated Biphenyls as Neuroendocrine Disruptors of Vasopressin Release: Effects during Physiological Activation In Vitro and Structure–Activity Relationships
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* Environmental Toxicology Graduate Program, University of California, Riverside, California 92521
Cellular and Molecular Toxicology Branch, Neurotoxicology Division, NHEERL, ORD, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711
Department of Cell Biology and Neuroscience, University of California, Riverside, California 92521
1 To whom correspondence should be addressed at Cellular and Molecular Toxicology Branch, Neurotoxicology Division, B 105-06, NHEERL/ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711. Fax: (919) 541-0717. E-mail: kodavanti.prasada{at}epa.gov.
Received January 17, 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 control, 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 and 5µM) 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 noncoplanarity 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.
Preliminary findings were presented at the 26th Symposium on Halogenated Environmental Organic Pollutants and POPs (Dioxin2006) meeting in Oslo, Norway (August 19–26, 2006).
The research described in this article has been reviewed by the National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the Agency nor does mention of trade names or commercial products constitute endorsement or recommendation for use.
M.C.C.C. and P.R.S.K. share equal last authorship on this paper.