Journal Article

Polybrominated Diphenyl Ethers and <i>ortho</i>-Substituted Polychlorinated Biphenyls as Neuroendocrine Disruptors of Vasopressin Release: Effects during Physiological Activation <i>In Vitro</i> and Structure–Activity Relationships

Cary G. Coburn, Margarita C. Currás-Collazo and Prasada Rao S. Kodavanti

in Toxicological Sciences

Volume 98, issue 1, pages 178-186
Published in print July 2007 | ISSN: 1096-6080
Published online April 2007 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfm086
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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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.

Keywords: polychlorinated biphenyls; polybrominated diphenyl ethers; neurotoxicity; supraoptic nucleus; neuroendocrine disruption; hypothalamus; intracellular signaling; organohalogen compounds; osmoregulation; structure–activity relationships

Journal Article.  5567 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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