Figure 2.

Building a case for neuroendocrine disruption. Environmental pollutants (e.g. , pesticides, PCBs, phthalates, pharmaceuticals, etc.) can act directly on cells within neuroendocrine tissues of the central nervous system (CNS) as well as on neurotransmitter systems that regulate neurohormone release, for example dopamine (DA), gamma-aminobutyric acid (GABA), norepinephrine (NE) and serotonin (5HT), among others. Altered neuropeptide synthesis and release will have downstream consequences on pituitary hormone release (arrow A), affecting homeostasis, growth and reproduction. Neuroendocrine disruptors are also proposed to regulate behaviors by modulating neuropeptide synthesis and release, the mechanisms of which are not fully characterized but likely involve membrane bound receptor (e.g., estrogen, progesterone) signaling and/or nuclear receptor (e.g., androgen, glucocorticoid, estrogen) pathways and post-translational protein modifications (i.e., phosphorylations) within neuroendocrine cells. Changes in behaviors (e.g., feeding, sociosexual) will adversely impact homeostasis, growth and reproductive output (arrow B). The CNS will be responsive to these physiological changes, and may be altered by longer acting effects of neuroendocrine disruptors, such epigenetic modifications (e.g., DNA methylation state) resulting in transgenerational effects (arrow C). Focused studies that address some of the questions proposed will assist to better define the scope of neuroendocrine disruption. Abbreviations: 5-HT, 5-hydroxytryptamine; GnRH, gonadotropin-releasing hormone; KP, kisspeptin; OXT, oxytocin (known as isotocin in fish), PCBs, polychlorinated biphenyls; PIT, pituitary; POA, preoptic area; TRH, thyrotropin-releasing hormone; VP, vasopressin.