Polybrominated diphenyl ethers and ortho-substituted polychlorinated biphenyls as neuroendocrine disruptors of vasopressin release: effects during physiological activation in vitro and structure-activity relationships
Abstract
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 5 microM) 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.
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PBDEs impair AVP release from the SON in response to dehydration and disrupt nitric oxide release related to AVP function in rats.
“Impaired AVP release from the SON in response to dehydration; disruption of nitric oxide release related to AVP function in rats”
From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [77]
The Discussion reports that the PBDE mixture DE-71 significantly reduced vasopressin (AVP) release from rat SON tissue punches during hyperosmotic stimulation, an in vitro model of the response to dehydration. It discusses nitric oxide as a possible mechanism but does not report measuring nitric oxide release or showing that PBDEs disrupt it. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPCBs impair AVP release from the SON in response to dehydration in rats.
“Impaired AVP release from the SON in response to dehydration in rats”
From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [77]
The PCB mixture Aroclor 1254 and PBDEs including DE-71 significantly reduced AVP release from the SON in response to dehydration in adult male rats.
“Work using adult male rats and SON tissue punches has yielded evidence that the PCB mixture Aroclor 1254 and the structurally related polybrominated flame retardants [polybrominated diphenyl ethers (PBDEs)], including the pentabrominated mixture DE-71, significantly reduced AVP release from the SON in response to dehydration (76, 77).”
From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [77]
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“Work using adult male rats and SON tissue punches has yielded evidence that the PCB mixture Aroclor 1254 and the structurally related polybrominated flame retardants [polybrominated diphenyl ethers (PBDEs)], including the pentabrominated mixture DE-71, significantly reduced AVP release from the SON in response to dehy…”
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Neuroendocrine effects of polychlorinated biphenyls (PCBs)
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Skrzynska, A. K., Martı́nez-Rodrı́guez, G., Gozdowska, M., Kulczykowska, E., Mancera, J. M., & Martos-Sitcha, J. A. (2019) · Aquatic Toxicology · doi:10.1016/j.aquatox.2019.04.019 · Cited by 6 · see citing works
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Kozlova, E. V., Denys, M. E., Bishay, A. E., Luna, C. N., Angelis, M. D., Campoy, L., Habbal, A., Lam, A. A., Luvsanravdan, N., Colton, A. G., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.07.28.667293 · Cited by 2 · see citing works
Toxicity mechanisms and interactions of polychlorinated biphenyls and polybrominated diphenylethers
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Neuroendocrine effects of brominated flame retardants, focused on polybrominated diphenyl ethers
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- Authors
- Coburn, C. G., Curras-Collazo, M. C., & Kodavanti, P. R. S.
- Affiliations
- University of California, Riverside (US)
- Environmental Protection Agency (US)
- Corresponding author
- Kodavanti, P. R. S.
- ORCID
- Kodavanti, P. R. S.
- Venue
- Toxicological Sciences
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-04-10
- Volume
- 98
- Issue
- 1
- Pages
- 178-186
- ISSN
- 1096-0929 (ISSN-L)
- 1096-6080
- OpenAlex
- W2164007706
- Cited by
- 45
- References
- 63
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 5 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 4 · 2015: 2 · 2014: 1 · 2013: 1 · 2012: 1
- FWCI
- 3.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicological Sciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Keywords
- polybrominated diphenyl ethers, vasopressin release, neuroendocrine disruption, supraoptic nucleus, paraventricular nucleus, flame retardants, DE-71, BDE-47, PCB 47, PCB 77, structure-activity relationship, osmotic stimulation, hypothalamus
- MeSH terms
- Animals, Biotransformation, Male, Neurosecretory Systems, Osmolar Concentration, Phenyl Ethers, Polybrominated Biphenyls, Polychlorinated Biphenyls, Species Specificity, Structure-Activity Relationship, Vasopressins, Rats, Sprague-Dawley, Chlorodiphenyl (54% Chlorine), Rats, Long-Evans, Rats, Endocrine Disruptors, Halogenated Diphenyl Ethers
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