Endocrine Disruption of Vasopressin Systems and Related Behaviors

Abstract

Endocrine disrupting chemicals (EDCs) are chemicals that interfere with the organizational or activational effects of hormones. Although the vast majority of the EDC literature focuses on steroid hormone signaling related impacts, growing evidence from a myriad of species reveals that the nonapeptide hormones vasopressin (AVP) and oxytocin (OT) may also be EDC targets. EDCs shown to alter pathways and behaviors coordinated by AVP and/or OT include the plastics component bisphenol A (BPA), the soy phytoestrogen genistein (GEN), and various flame retardants. Many effects are sex specific and likely involve action at nuclear estrogen receptors. Effects include the elimination or reversal of well-characterized sexually dimorphic aspects of the AVP system, including innervation of the lateral septum and other brain regions critical for social and other non-reproductive behaviors. Disruption of magnocellular AVP function has also been reported in rats, suggesting possible effects on hemodynamics and cardiovascular function.

CLARITY‐BPA academic laboratory studies identify consistent low‐dose Bisphenol A effects on multiple organ systems

“…Numerous genes involved in glutamate signalling were also found to be disrupted in the amygdala. Collectively, these data are consistent with prior work by Patisaul and others showing that BPA impacts oestrogen, oxytocin and vasopressin pathways throughout the brain …”

“…As discussed in the Section 1, BPA effects are known to be mediated through multiple cellular receptors and signalling pathways. 14,15 As BPA engagement of these multiple receptors/pathways occurs at widely different doses (low-dose for membrane receptor pathways; high-dose activation/antagonism for nuclear receptors), one would expect to observe non-linear BPA effects across increasing doses, 131 as is seen in a considerable number of end-points in the CLARITY-BPA studies. Further, expression of the different receptors varies widely across organs and cell types which can lead to dose-selective responses in different organs within the same animals.…”

“…Collectively, these data are consistent with prior work by Patisaul and others showing that BPA impacts oestrogen, oxytocin and vasopressin pathways throughout the brain. 15,45,48,[58][59][60] In summary, the CLARITY-BPA studies, and the two collaborative studies with NCTR that proceeded them, confirm that developmental exposure to BPA, at doses as low as 2.5 μg/kg BW/d, can alter ER expression in the brain. Directionality differs with age with heightened expression generally observed in neonates and suppressed expression observed in adolescents.…”

“…Specifically, BPA acts as an agonist of membrane and nuclear oestrogen receptors (ERs), and an antagonist of thyroid hormone receptor and androgen receptor signalling . There is also some evidence that it can disrupt other signalling pathways including neuropeptide and GABA signalling …”

“…14 There is also some evidence that it can disrupt other signalling pathways including neuropeptide and GABA signalling. 15 More than 100 human epidemiology studies have examined associations between BPA exposures and human diseases. 16 Although these studies individually have limitations, they collectively suggest that current levels of exposure are associated with adverse health outcome.…”