Environmental chemicals and thyroid function

Abstract

There is growing evidence that environmental chemicals can disrupt endocrine systems. Most evidence originates from studies on reproductive organs. However, there is also suspicion that thyroid homeostasis may be disrupted. Several groups of chemicals have potential for thyroid disruption. There is substantial evidence that polychlorinated biphenyls, dioxins and furans cause hypothyroidism in exposed animals and that environmentally occurring doses affect human thyroid homeostasis. Similarly, flame retardants reduce peripheral thyroid hormone (TH) levels in rodents, but human studies are scarce. Studies also indicate thyroid-disruptive properties of phthalates, but the effect of certain phthalates seems to be stimulative on TH production, contrary to most other groups of chemicals. Thyroid disruption may be caused by a variety of mechanisms, as different chemicals interfere with the hypothalamic -pituitary -thyroid axis at different levels. Mechanisms of action may involve the sodium-iodide symporter, thyroid peroxidase enzyme, receptors for THs or TSH, transport proteins or cellular uptake mechanisms. The peripheral metabolism of the THs can be affected through effects on iodothyronine deiodinases or hepatic enzymes. Even small changes in thyroid homeostasis may adversely affect human health, and especially fetal neurological development may be vulnerable. It is therefore urgent to clarify whether the animal data showing effects of chemicals on thyroid function can be extended to humans. European Journal of Endocrinology 154 599-611

Exposure to DE-71 alters thyroid hormone levels and gene transcription in the hypothalamic–pituitary–thyroid axis of zebrafish larvae

“…Environmental chemicals that interfere with TH synthesis have attracted great attention in recent studies (e.g., Boas et al, 2006;Zoeller et al, 2007a,b;Lema et al, 2008;Richardson et al, 2008;Li et al, 2009;Porazzi et al, 2009;Morgado et al, 2009;Szabo et al, 2009). We developed a model in which zebrafish embryos were exposed to DE-71 until 14 dpf and evaluated the embryos for TH disruption.…”

“…In addition, albumin and thyroxine-binding globulin (TBG) are also binding to THs in fish plasma (Lema et al, 2008). Several environmental contaminants (e.g., some metabolites and derivatives of PCBs and phenol compounds), which exhibit structural resemblance to THs, may influence the levels of circulating THs in vertebrates by competing for their binding sites on transport proteins and interfering with TH homeostasis by binding TTR (Boas et al, 2006;Morgado et al, 2009). Therefore, the chemicals that interfere with the binding of TH to TTR may directly influence the concentration of free THs in the plasma and the plasma clearance rate of THs in fish.…”

“…Hence, substances interfering with TH activity can seriously compromise the normal development of the exposed species and may have profound consequences on their fitness and survival (Boas et al, 2006). In zebrafish, THs are necessary for the transition from the embryonic to larval stage and from the larval to the juvenile stage (Liu and Chan, 2002).…”

Structure–activity relations in binding of perfluoroalkyl compounds to human thyroid hormone T3 receptor

“…There are several different TH physiological steps PFCs may interfere with, such as TH biosynthesis, transport, metabolism, or action on receptor pathways in target cells (Boas et al 2006). Earlier mechanistic studies suggest that PFCs might reduce serum THs levels by reducing the responsiveness of the hypothalamuspituitary-thyroid axis or by displacing circulating THs from the transport proteins such as transthyretin and albumin (Gutshall et al 1989;Chen and Guo 2009;Weiss et al 2009).…”

Identification of Thyroid-Receptor Antagonists in Water from the Guanting Reservoir, Beijing, China

“…Thus, maintaining normal thyroid function is essential for psychological and physiological well-being (Boas et al 2012). However, increasing evidence from animal and in vitro studies indicates that the thyroid is vulnerable to endocrine-disrupting effects (Boas et al 2006;Sciarrillo et al 2008). Industrial chemicals characterized as thyroiddisrupting chemicals (TDCs) include the following: polychlorinated biphenyls (PCBs), dioxins, brominated flame retardants (BFRs), pesticides, perfluorinated chemicals (PFCs), phenols, phthalate esters (PAEs), and perchlorate (Boas et al 2012;Botelho et al 2009).…”