title: Developmental thyroid hormone disruption: prevalence, environmental contaminants and neurodevelopmental consequences.
abstract: Thyroid hormones (TH) are critical for growth and development and particularly brain development. There are numerous environmental agents that lead to marginal reductions of circulating TH. Although it is clear that severe developmental hypothyroidism is profoundly detrimental to neurodevelopment, there is less information regarding the consequences of modest degrees of thyroid. The impact of low level TH disruptions induced by environmental contaminants has not been defined. This paper is a synopsis from four invited speakers who presented at the 13th International Neurotoxicology Association meeting held in Xi'an, China during the summer of 2011. An overview of the role of TH in brain development and a review of human and animal data on the neurological sequelae of disruption of the thyroid axis in the pre- and early post-natal periods were presented by Mary Gilbert and Joanne Rovet. Iodine deficiency, a common cause of TH insufficiency and mental retardation in many countries, including China, was addressed by Zupei Chen. In this presentation the current incidence of iodine deficiency and neurological outcome in China and the efficacy of recently implemented iodinization programs to eliminate this cause of mental retardation were reviewed. Joanne Rovet described the impact of TH disruption during pregnancy and under conditions of congenital hypothyroidism. Children born with normal thyroid function, but who experienced TH insufficiency in the womb, display subtle cognitive impairments and abnormalities in brain imaging. Despite early detection and treatment, deficiencies also exist in children born with thyroid disorders. Different patterns of cognitive effects result from prenatal versus postnatal TH insufficiency. Mary Gilbert reported on the effects of environmental contaminants with thyroid disrupting action on brain development in animals. Results of neurophysiological, behavioral, structural and molecular alterations that accompany modest perturbations of the thyroid axis were reviewed. Noriyuki Koibuchi described molecular targets of TH-mediated signalling accompanying exposure to persistent organic pollutants. Both polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are prevalent environmental contaminants that disrupt TH signalling at the receptor level. This action by these chemical classes could contribute to the negative impact of these chemicals on brain function. In summary, epidemiological, preclinical and animal research has clearly identified the critical role of TH in brain development. Additional work is required to understand the impact of low level perturbations of the thyroid axis to evaluate the risk associated with environmental contaminants with thyroid action.
authors.affiliation: Toxicity Assessment Division (MD-B105-05), US Environmental Protection Agency, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC 27711, USA. gilbert.mary@epa.gov
authors.forename: Mary E
authors.initials: ME
authors.lastname: Gilbert
authors.forename: Joanne
authors.initials: J
authors.lastname: Rovet
authors.forename: Zupei
authors.initials: Z
authors.lastname: Chen
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Koibuchi
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003409:Congenital Hypothyroidism / Q000453:epidemiology / Q000517:prevention & control; D052244:Endocrine Disruptors / Q000009:adverse effects*; D004781:Environmental Exposure / Q000009:adverse effects*; D004785:Environmental Pollutants / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007455:Iodine / Q000008:administration & dosage / Q000172:deficiency; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects; D055495:Neurogenesis / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000453:epidemiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D015995:Prevalence; D018570:Risk Assessment; D012307:Risk Factors; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage; D013963:Thyroid Hormones / Q000378:metabolism*
chemical_list: D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D017673:Sodium Chloride, Dietary; D013963:Thyroid Hormones; C034024:iodized salt; D007455:Iodine