Endocrine Disrupters: A Review of Some Sources, Effects, and Mechanisms of Actions on Behaviour and Neuroendocrine Systems
Abstracts
Exposure to EDCs during critical phases of development may result in more salient effects on neurodevelopmental and/or reproductive processes
Some environmental contaminants interact with hormones and may exert adverse consequences due to their actions as endocrine disrupting chemicals (EDCs). Exposure in people is typically due to contamination of the food chain, inhalation of contaminated house dust, or occupational exposure. EDCs include pesticides and herbicides (such as diphenyl-dichloro-trichloroethane, DDT, or its metabolites), methoxychlor, biocides, heat stabilizers and chemical catalysts (such as tributyltin, TBT), plastic contaminants (e.g. bisphenol A, BPA), pharmaceuticals (i.e. diethylstilbestrol, DES; 17alpha-ethynilestradiol, EE2), or dietary components (such as phytoestrogens).
The goal of this review is to address sources, effects and actions of EDCs, with an emphasis on topics discussed at the International Congress on Steroids and the Nervous System. EDCs may alter reproductively-relevant or non-reproductive, sexually-dimorphic behaviors. In addition, EDCs may have significant effects on neurodevelopmental processes, influencing morphology of sexually-dimorphic cerebral circuits. Exposure to EDCs is more dangerous if it occurs during specific “critical periods” of life, such as intrauterine, perinatal, juvenile or puberty periods, when organisms are more sensitive to hormonal disruption, than in other periods. However, exposure to EDCs in adulthood also can alter physiology. Several EDCs are xenoestrogens, may alter serum lipid concentrations, or metabolism enzymes that are necessary for converting cholesterol to steroid hormones, ultimately altering production of E2 and/or other steroids. Finally, many EDCs may have actions via, or independent of, classic actions at cognate steroid receptors. EDCs may have effects through numerous other substrates, such as the aryl hydrocarbon receptor (AhR), the peroxisome proliferator-activated receptor (PPAR) and retinoid X receptor (RXR), signal transduction pathways, calcium influx, and/or neurotransmitter receptors.
Thus, EDCs, from varied sources, may have organizational effects during development, and/or activational effects in adulthood, that influence sexually-dimorphic, reproductively-relevant processes or other functions, by mimicking, antagonizing, or altering steroidal actions.
Sources of Contaminants
“Some individuals have also been exposed to contaminants with adverse effects due to medical (diethylstilbestrol; DES),…”
EDCs’ Effects on Neurodevelopmental Processes
“Notably, there are significant increases in the incidence of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders. Development of psychological disorders with sex-biased prevalence rates may be associated with the disruption of developmental trajectory and/or maturation of the sexually-dimorphic brain. Autism spectrum disorders (44), attention deficit disorder, and depression, are disorders with sex-biased prevalence rates. Disruption of hormonally-controlled, sexual differentiation of the brain, may increase vulnerability for these, or other, sexually-dimorphic functions. Exposure to endocrine disrupters e.g., PCBs, BPA that disrupt hormone function during critical periods of prenatal development may influence susceptibility to sex- and/or hormonally-differentiated aspects of behavior. Males are more vulnerable to these disorders, which have salient motor and arousal components. Thus, the increase in the incidence of these disorders may reflect effects of EDCs on male-typical levels of arousal and/or stress responsiveness.”
EDCs Influence Brain Morphology
“In the Japanese quail, embryonic exposure to different EDCs (DES, genistein, or DDE) induced a significant demasculinization of the sexually dimorphic parvocellular AVT system.”
Obesogenic effects of EDCs
“One notable obesogen is DES, a synthetic estrogen initially prescribed to pregnant women to prevent miscarriage but ultimately distributed more widely before its use was discontinued in the late 1970’s because prenatal exposure was linked to a higher risk of vaginal. Children exposed in utero are unfortunately at higher risk for a wide range of neuroendocrine disorders including reproductive malformations, infertility and testicular cancer. Emerging evidence now suggests that this population may also be at greater risk for obesity and metabolic disorders.”
- Read and download the full study (free access) Endocrine Disrupters: A Review of Some Sources, Effects, and Mechanisms of Actions on Behaviour and Neuroendocrine Systems, on the NCBI, PubMed, PMC3245362, 2012 Jan.
- Image credit frenji’s adventures.
DES DIETHYLSTILBESTROL RESOURCES
- Studies on DES and ADHD, autism, Down’s Syndrome.
- Diethylstilbestrol DES studies by topics.